Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease

Alzheimer’s disease is a neurodegenerative disorder accounting for more than 50% of cases of dementia. Diagnosis of Alzheimer’s disease relies on cognitive tests and analysis of amyloid beta, protein tau, and hyperphosphorylated tau in cerebrospinal fluid. Although these markers provide relatively high sensitivity and specificity for early disease detection, they are not suitable for monitor of disease progression. In the present study, we used label-free shotgun mass spectrometry to analyse the cerebrospinal fluid proteome of Alzheimer’s disease patients and non-demented controls to identify potential biomarkers for Alzheimer’s disease. We processed the data using five programs (DecyderMS, Maxquant, OpenMS, PEAKS, and Sieve) and compared their results by means of reproducibility and peptide identification, including three different normalization methods. After depletion of high abundant proteins we found that Alzheimer’s disease patients had lower fraction of low-abundance proteins in cerebrospinal fluid compared to healthy controls (p<0.05). Consequently, global normalization was found to be less accurate compared to using spiked-in chicken ovalbumin for normalization. In addition, we determined that Sieve and OpenMS resulted in the highest reproducibility and PEAKS was the programs with the highest identification performance. Finally, we successfully verified significantly lower levels (p<0.05) of eight proteins (A2GL, APOM, C1QB, C1QC, C1S, FBLN3, PTPRZ, and SEZ6) in Alzheimer’s disease compared to controls using an antibody-based detection method. These proteins are involved in different biological roles spanning from cell adhesion and migration, to regulation of the synapse and the immune system.
Regulation of Pseudomonas aeruginosa virulence factors by two novel RNA thermometers

Significance Several bacteria that are pathogens of humans regulate the production of virulence factors in response to temperature changes, expressing them only at 37 °C. This thermoregulation is commonly due to the presence of RNA structures (RNA thermometers) in the 5′ regions of transcripts specifying regulatory proteins responsible for the expression of virulence-associated traits. At environmental conditions, RNA thermometers possess structures that block translation initiation of mRNAs, whereas at body temperature these structures are no longer stable, allowing the synthesis of their corresponding proteins. We report for the first time, to our knowledge, the molecular basis of thermoregulation of virulence-factor production in the opportunistic pathogen Pseudomonas aeruginosa, and have determined that this regulation is achieved by two RNA thermometers with previously unidentified characteristics not previously reported in bacteria. In a number of bacterial pathogens, the production of virulence factors is induced at 37 °C; this effect is often regulated by mRNA structures formed in the 5′ untranslated region (UTR) that block translation initiation of genes at environmental temperatures. At 37 °C, the RNA structures become unstable and ribosomes gain access to their binding sites in the mRNAs. Pseudomonas aeruginosa is an important opportunistic pathogen and the expression of many of its virulence-associated traits is regulated by the quorum-sensing (QS) response, but the effect of temperature on virulence-factor expression is not well-understood. The aim of this work is the characterization of the molecular mechanism involved in thermoregulation of QS-dependent virulence-factor production. We demonstrate that traits that are dependent on the QS transcriptional regulator RhlR have a higher expression at 37 °C, correlating with a higher RhlR concentration as measured by Western blot. We also determined, using gene fusions and point mutations, that RhlR thermoregulation is a posttranscriptional effect dependent on an RNA thermometer of the ROSE (Repression Of heat-Shock gene Expression) family. This RNA element regulates the expression of the rhlAB operon, involved in rhamnolipid production, and of the downstream rhlR gene. We also identified a second functional thermometer in the 5′ UTR of the lasI gene. We confirmed that these RNA thermometers are the main mechanism of thermoregulation of QS-dependent gene expression in P. aeruginosa using quantitative real-time PCR. This is the first description, to our knowledge, of a ROSE element regulating the expression of virulence traits and of an RNA thermometer controlling multiple genes in an operon through a polar effect.
Sequential gene expression of P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP) and lung resistance protein: functional activity of P-gp and MRP present in the doxorubicin-resistant human K562 cell lines

Previous studies have reported that P-glycoprotein (P-gp), a transmembrane efflux pump involved in multidrug resistance (MDR), was overexpressed in the doxorubicin (Dox)-resistant human erythroleukemia cell line K562. Nevertheless, several results suggested that P-gp was not the only mechanism involved in these resistant cells. Sequential co-expression of other MDR-associated proteins was sometimes reported, as MDR-associated protein (MRP) and lung resistance protein (LRP), in different MDR cell lines. Thus, mRNA expression and stability of P-gp, MRP and LRP were analyzed, while their corresponding protein levels were quantified in correlation with functional assay, in the K562 cell line and two Dox-resistant variants (K562/R). Their P-gp content was in accordance with their degree of resistance, but not as much in the level of mRNA expression, suggesting a post-transcriptional regulation. On the other hand, MRP could play a minor role in MDR because of an unchanged expression in K562/R sublines. A surprising progressive disappearance of LRP in both resistant cells suggested that the original mechanism of drug redistribution may be operative, involving a negative role for LRP.
Diversity of gene expression in adenocarcinoma of the lung

The global gene expression profiles for 67 human lung tumors representing 56 patients were examined by using 24,000-element cDNA microarrays. Subdivision of the tumors based on gene expression patterns faithfully recapitulated morphological classification of the tumors into squamous, large cell, small cell, and adenocarcinoma. The gene expression patterns made possible the subclassification of adenocarcinoma into subgroups that correlated with the degree of tumor differentiation as well as patient survival. Gene expression analysis thus promises to extend and refine standard pathologic analysis.
The Puerto Princesa Underground River (Palawan, Philippines): some peculiar features of a tropical, high-energy coastal karst system

Abstract The Puerto Princesa Underground River, amongst the largest caves of the Philippine Islands, is the most visited show cave in the country, even though it has undergone no tourism adaptation at all. Its scientific importance primarily relies on the fact that it is one of the largest known underground estuaries in the world, and the effect of tides is visible along more than 7 km of the cave length. The complex relationships between sea and freshwater influence not only the hydrodynamics of the system and the speleogenetic processes presently active, but also its climate and its ecosystem. The systematic exploration and research of this coastal karst system started some 40 years ago and have shown that the Puerto Princesa Underground River is one of the most important caves in the world with regard to many different scientific fields. Speleogenesis concerns the initial phreatic solution followed by vadose erosion with periodical marine invasion, and subsequent saline/freshwater-mixing processes during sea-level highstands. The hydrodynamic behaviour of the water flowing inside the cave is rather complex, being simultaneously controlled by allogenic recharge and tides. Speleothems abundantly occur with several forms, some of which have never been described before. Several minerals, some of which are very rare, are present, together with palaeontological remains exposed by differential corrosion on rock walls. Last but not least, two large populations of bats and swiftlets sustain a complex subterranean ecosystem.
The limited link between accommodation space, sediment thickness, and inner platform facies distribution (Holocene–Pleistocene, Bahamas)

Cyclic facies variations in shallow‐water carbonate platforms often show repetitive facies patterns that are frequently interpreted to reflect the sedimentary response to variations in sea‐level related to changes in climate linked to orbital variations, the Milankovitch frequencies. Whether these shallow‐marine carbonates represent a complete infill of accommodation space, or are subtidal cycles, has been discussed in numerous papers. The extent to which the thickness of a single depositional cycle is a direct measure of the amplitude of relative sea‐level change is not fully understood. New shallow seismic data from Great Bahama Bank reveal that accommodation space created during the Holocene sea‐level rise is not filled in a predictable way. Three seismic horizons were identified: the seabed, the Pleistocene top, and a horizon within the Pleistocene. Depth surface and thickness maps of the Holocene and Pleistocene layers were combined with 326 in situ water‐depth measurements to assess the upper limit of the present accommodation space. The analysis showed that accommodation space and Holocene sediment thickness, and water depth are not correlated. In addition, the actual water depth and inner platform facies distribution showed no straightforward link. The energy distribution across the shallow‐water platform appears to control the facies type rather than water depth. Mud‐dominated sediments prevail in shallow low‐energy areas protected by a topographic barrier, whereas mud‐free coarse‐grained sediments mainly occur in deeper areas with hydrodynamic energy induced by strong tidal currents, ocean water influx, and winds. Hence, the uneven energy distribution not only results in unpredictable differences in the carbonate‐cycle thickness on the platform but also to a water depth independent facies distribution pattern within the inner platform. Therefore, care should be taken when deducing sea‐level signals from inner platform facies distribution and sediment thickness patterns on ancient platforms.
Predicting In Silico Which Mixtures of the Natural Products of Plants Might Most Effectively Kill Human Leukemia Cells?

The aim of the analysis of just 13 natural products of plants was to predict the most likely effective artificial mixtures of 2-3 most effective natural products on leukemia cells from over 364 possible mixtures. The natural product selected included resveratrol, honokiol, chrysin, limonene, cholecalciferol, cerulenin, aloe emodin, and salicin and had over 600 potential protein targets. Target profiling used the Ontomine set of tools for literature searches of potential binding proteins, binding constant predictions, binding site predictions, and pathway network pattern analysis. The analyses indicated that 6 of the 13 natural products predicted binding proteins which were important targets for established cancer treatments. Improvements in effectiveness were predicted for artificial combinations of 2 or 3 natural products. That effect might be attributed to drug synergism rather than increased numbers of binding proteins bound (dose effects). Among natural products, the combinations of aloe emodin with mevinolin and honokiol were predicted to be the most effective combination for AML-related predicted binding proteins. Therefore, plant extracts may in future provide more effective medicines than the single purified natural products of modern medicine, in some cases.
Associations between physical and psychological problems in a group of patients with stress-related behavior and somatoform disorders

The research questions in this study were: How do patients with stress-related behavior and somatoform disorders assess symptoms and self-image compared to healthy individuals, and how are these assessments related to bodily resources, assessed with a physiotherapeutic body examination? The test group (n = 31) consisted of consecutive patients referred to a treatment center specializing in psychosomatic problems. Significant differences (p ≤ 0.01) were found between the test and comparison group (n = 22) on all but two of the ten subscales of the Resource-Oriented Body Examination (ROBE II). This was also the case for all the subscales of The Symptom Checklist-90(SCL-90; comparison group n = 52), and for all but three of the eight clusters of the Structural Analysis of Social Behavior (SASB) (comparison group n = 52). For the patient group, the ROBE II subscale Increased respiratory control correlated significantly with the SCL-90 subscales that measures Anger-hostility, Phobic anxiety, Paranoid ideation, with the Personality Severity Index (PSI) and with the SASB clusters Daydreaming and self-neglect, Self-indictment and oppression with r's between 0.38 and 0.50. Body examination with ROBE II might provide a useful assessment tool in patients whose stress-related problems appear to contain associations between psychological and physical problems.
Matches, Mismatches, and Methods: Multiple-View Workflows for Energy Portfolio Analysis

The energy performance of large building portfolios is challenging to analyze and monitor, as current analysis tools are not scalable or they present derived and aggregated data at too coarse of a level. We conducted a visualization design study, beginning with a thorough work domain analysis and a characterization of data and task abstractions. We describe generalizable visual encoding design choices for time-oriented data framed in terms of matches and mismatches, as well as considerations for workflow design. Our designs address several research questions pertaining to scalability, view coordination, and the inappropriateness of line charts for derived and aggregated data due to a combination of data semantics and domain convention. We also present guidelines relating to familiarity and trust, as well as methodological considerations for visualization design studies. Our designs were adopted by our collaborators and incorporated into the design of an energy analysis software application that will be deployed to tens of thousands of energy workers in their client base.
Column Separation in a Shut-In Liquid Hydrocarbon Transmission Pipeline

Crude oil transportation pipelines depend on Computational Pipeline Monitoring (CPM) systems for leak detection. Accurate prediction of the volume of vapor phase in the pipeline is very challenging when crude oil goes though phase change (column separation) in the pipeline. It is also challenging to accurately predict the vapor phase volume when the pipeline is started from extended shut-in period during which thermal cooling or heating can occur depending on the season of the year. Pipeline operators rely on the accuracy of CPMs to make decisions on column separation and to avoid the masking of a leak during column separation. The column separation can happen due to heating and/or cooling during extended pipeline shut-in, or due to elevation changes or due to flow transients. New methods of approach to address the hydraulics are necessary when dealing with a pipeline during shut-in period. Particularly a shut-in pipeline has no longitudinal motion of fluid, however phase change occurrence attempts to set the stationary fluid inside a pipe into motion and overcoming this difficulty was not available in the literature perhaps due to lack of encumberment with similar problems. This paper explains mechanism of column separation and its transients in pipelines during extended shut-in period. The results for a 90 Km long-pipeline shut-in over a 78-hour period will be presented to show the evolution of flow field and column separation (vapor phase change) prediction and hydrodynamic pressure in the whole pipeline over the shut-in period. This paper will also critically review the current approaches available in the literature to predict the column separation.
The Water Budget Myth Revisited: Why Hydrogeologists Model

Within the ground water community, the idea persists that if one can estimate the recharge to a ground water system, one then can determine the size of a sustainable development. Theis addressed this idea in 1940 and showed it to be wrong‐yet the myth continues. The size of a sustainable ground water development usually depends on how much of the discharge from the system can be “captured” by the development. Capture is independent of the recharge; it depends on the dynamic response of the aquifer system to the development. Ground water models were created to study the response dynamics of ground water systems; it is one of the principal reasons hydrogeologists model.
Traumatic axonal injury: Relationships between lesions in the early phase and diffusion tensor imaging parameters in the chronic phase of traumatic brain injury

This prospective study of traumatic brain injury (TBI) patients investigates fractional anisotropy (FA) from chronic diffusion tensor imaging (DTI) in areas corresponding to persistent and transient traumatic axonal injury (TAI) lesions detected in clinical MRI from the early phase. Thirty‐eight patients (mean 24.7 [range 13–63] years of age) with moderate‐to‐severe TBI and 42 age‐ and sex‐matched healthy controls were included. Patients underwent 1.5‐T clinical MRI in the early phase (median 7 days), including fluid‐attenuated inversion recovery (FLAIR) and T2* gradient echo (T2*GRE) sequences. TAI lesions from the early phase were characterized as nonhemorrhagic or microhemorrhagic. In the chronic phase (median 3 years), patients and controls were imaged at 3 T with FLAIR, T2*GRE, T1, and DTI sequences. TAI lesions were classified as transient or persistent. The FLAIR/T2*GRE images from the early phase were linearly registered to the FA images from the chronic phase and lesions manually segmented on the FA‐registered FLAIR/T2*GRE images. For regions of interest (ROIs) from both nonhemorrhagic and microhemorrhagic lesion, we found a significant linear trend of lower mean FA from ROIs in healthy controls to ROIs in patients without either nonhemorrhagic or microhemorrhagic lesions and further to transient and finally persistent lesion ROIs (P < 0.001). Histogram analyses showed lower FA in persistent compared with transient nonhemorrhagic lesion ROIs (P < 0.001), but this was not found in microhemorrhagic lesion ROIs (P = 0.08–0.55). The demonstrated linear trend of lower FA values from healthy controls to persistent lesion ROIs was found in both nonhemorrhagic and microhemorrhagic lesions and indicates a gradual increasing disruption of the microstructure. Lower FA values in persistent compared with transient lesions were found only in nonhemorrhagic lesions. Thus, clinical MRI techniques are able to depict important aspects of white matter pathology across the stages of TBI. © 2016 Wiley Periodicals, Inc.
An Information-Theoretic Analysis of Thompson Sampling

We provide an information-theoretic analysis of Thompson sampling that applies across a broad range of online optimization problems in which a decision-maker must learn from partial feedback. This analysis inherits the simplicity and elegance of information theory and leads to regret bounds that scale with the entropy of the optimal-action distribution. This strengthens preexisting results and yields new insight into how information improves performance.
Prevention of Arterial Reocclusion After Thrombolysis With Recombinant Lipoprotein‐Associated Coagulation Inhibitor

BackgroundThis study was designed to determine whether arterial reocclusion after thrombolysis can be prevented by lipoprotein-associated coagulation inhibitor (LACI), a physiological inhibitor of tissue factor-induced coagulation mediated by the extrinsic pathway. Methods and ResultsThrombosis was induced in femoral arteries of anesthetized dogs with the use of anodal current to elicit extensive vascular injury and formation of platelet-rich thrombi in one artery and with thrombogenic copper wire to elicit fibrin-rich thrombi without appreciable vascular injury in the contralateral artery. Recanalization of both vessels was induced with t-PA (1.7 mg/kg i.v. over 1 hour) and verified with Doppler flow probes. Reocclusion occurred within 2 hours in seven of seven arteries with electrical injury-induced thrombosis and in four of seven arteries with copper wire-induced thrombosis in the absence of LACI. In dogs given infusions of recombinant DNA-produced LACI (225 pug/kg over 15 minutes, followed by 4 jig/kg/min i.v.) after completion of the infusion of t-PA, no reocclusion occurred during the 2-hour interval of observation in any of the five arteries subjected to electrical injury (p < 0.001), and cyclic partial occlusions were nearly abolished (0.4 ± 0.4/hr in LACI-treated dogs compared with 13.7 ± 5.5/hr in saline-treated dogs, p' < 0.0001). In contrast, reocclusion occurred in two of five arteries with indwelling copper wires, and cyclic partial occlusions were unaffected despite LACI. LACI prolonged the partial thromboplastin time modestly (1.7±0.2 xbaseline) but did not affect platelet counts or aggregation assessed ex vivo. ConclusionsInhibition of the extrinsic pathway of coagulation with LACI prevents thrombotic arterial reocclusion after thrombolysis in vessels subjected to extensive vascular injury. Our results demonstrate that activation of the extrinsic pathway plays a critical role in thrombotic reocclusion and that LACI provides a highly targeted approach to facilitate sustained recanalization without directly inhibiting platelets.
Factors associated with HIV seroconversion in gay men in England at the start of the 21st century

Objectives: To detect and quantify current risk factors for HIV seroconversion among gay men seeking repeat tests at sexual health clinics. Design: Unmatched case control study conducted in London, Brighton and Manchester, UK. Methods: 75 cases (recent HIV positive test following a negative test within the past 2 years) and 157 controls (recent HIV negative test following a previous negative test within the past 2 years) completed a computer-assisted self interview focused on sexual behaviour and lifestyle between HIV tests. Results: Cases and controls were similar in socio-demographics, years since commencing sex with men, lifetime number of HIV tests, reasons for seeking their previous HIV tests and the interval between last HIV tests (mean = 10.5 months). Risk factors between tests included unprotected receptive anal intercourse (URAI) with partners not believed to be HIV negative (adjusted odds ratio (AOR) and 95% confidence interval 4.1, 1.8 to 9.3), where increased risk was associated with concomitant use of nitrite inhalants, receiving ejaculate and increasing numbers of partners. Independent risk was also detected for unprotected insertive anal intercourse (UIAI) with more than one man (AOR 2.7, 1.3 to 5.5) and use of nitrite inhalants (AOR 2.4, 1.1 to 5.2). Conclusions: HIV serodiscordant unprotected anal intercourse remains the primary context for HIV transmission among gay men, with increased risk associated with being the receptive partner, receiving ejaculate and use of nitrite inhalants. Although the HIV transmission risk of URAI is widely acknowledged, this study highlights the risk of UIAI and that nitrite inhalants may be an important facilitator of transmission when HIV exposure occurs.