Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular characterization of a mutation affecting abscisic acid biosynthesis and consequently stomatal responses to humidity in an agriculturally important species

Mutants deficient in the phytohormone abscisic acid (ABA) have been instrumental physiological models for understanding both the biosynthesis and action of this critical hormone. The wilty mutant of the agriculturally important species Pisum sativum is a quintessential ABA deficient mutant which has remained molecularly uncharacterised in the 40 years since its discovery. We show that the wilty mutation affects the xanthoxin dehydrogenase step in the ABA biosynthetic pathway and that this step in ABA biosynthesis is critical for normal stomatal responses to changes in humidity.
SIZE DISTRIBUTION OF SPONTANEOUSLY FORMED LIPOSOMES BY THE ALCOHOL INJECTION METHOD

ABSTRACT A dynamic light scattering study of the size distribution of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) liposomes formed by the injection method is presented. By this method, an aliquot of methanol stock solution containing the surfactant is injected into water. The main aim of the present work was to determine under which conditions a monomodal and narrow size distribution could be obtained. The influence of several parameters on the size distribution was investigated. Firstly, we examined the influence of the POPC concentration in the initial stock methanol solution, when the POPC concentration in the final aqueous solution remains constant; secondly, the influence of POPC concentration in the aqueous phase, while the lipid concentration in the stock methanol remains constant. In both cases narrow monomodal size distributions of liposomes, centered between 40 and 70 nm, are obtained at low concentrations of POPC, in the stock methanol solution (≤25 mM) as well as in the final aqueous solution. However, at a higher lipid concentration range a more complex size distribution is observed, and an additional component larger than 500 nm is detected. The effect of dilution was also studied. It can be shown that dilution of the more concentrated POPC solutions determines the disappearance of the larger component, which is then ascribed to aggregates or clusters of smaller liposomes. Interestingly, by concentrating the diluted, monomodal liposomal suspensions, the monomodal distribution is maintained. Concentrated liposome preparations can therefore be obtained having only one population of liposomes centered around 40–70 nm radii. Finally, the effect of aging was studied. It appears that the larger components in the light scattering results are not time-stable, whereas the smaller liposome species are. It is shown that these features are also present when alcohols different from methanol are used.
miR-21 Promotes Human Nucleus Pulposus Cell Proliferation through PTEN/AKT Signaling

The precise role of nucleus pulposus cell proliferation in the pathogenesis of intervertebral disc degeneration remains to be elucidated. Recent findings have revealed that microRNAs, a class of small noncoding RNAs, may regulate cell proliferation in many pathological conditions. Here, we showed that miR-21 was significantly upregulated in degenerative nucleus pulposus tissues when compared with nucleus pulposus tissues that were isolated from patients with idiopathic scoliosis and that miR-10b levels were associated with disc degeneration grade. Moreover, bioinformatics target prediction identified PTEN as a putative target of miR-21. miR-21 inhibited PTEN expression by directly targeting the 3′UTR, and this inhibition was abolished through miR-21 binding site mutations. miR-21 overexpression stimulated cell proliferation and AKT signaling pathway activation, which led to cyclin D1 translation. Additionally, the increase in proliferation and cyclin D1 expression induced by miR-21 overexpression was almost completely blocked by Ly294002, an AKT inhibitor. Taken together, aberrant miR-21 upregulation in intervertebral disc degeneration could target PTEN, which would contribute to abnormal nucleus pulposus cell proliferation through derepressing the Akt pathway. Our study also underscores the potential of miR-21 and the PTEN/Akt pathway as novel therapeutic targets in intervertebral disc degeneration.
Properties and Applications of Programs with Monotone and Convex Constraints

We study properties of programs with monotone and convex constraints. We extend to these formalisms concepts and results from normal logic programming. They include the notions of strong and uniform equivalence with their characterizations, tight programs and Fages Lemma, program completion and loop formulas. Our results provide an abstract account of properties of some recent extensions of logic programming with aggregates, especially the formalism of lparse programs. They imply a method to compute stable models of lparse programs by means of off-the-shelf solvers of pseudo-boolean constraints, which is often much faster than the smodels system.
Nutritional status influences generic and disease-specific quality of life measures in haemodialysis patients.

BACKGROUND Poor nutritional status and worse healthrelated quality of life (QoL) have been reported in haemodialysis (HD) patients. The utilization of generic and disease specific QoL questionnaires in the same population may provide a better understanding of the significance of nutrition in QoL dimensions. OBJECTIVE To assess nutritional status by easy to use parameters and to evaluate the potential relationship with QoL measured by generic and disease specific questionnaires. METHODS Nutritional status was assessed by subjective global assessment adapted to renal patients (SGA), body mass index (BMI), nutritional intake and appetite. QoL was assessed by the generic EuroQoL and disease specific Kidney Disease Quality of Life-Short Form (KDQoL-SF) questionnaires. RESULTS The study comprised 130 patients of both genders, mean age 62.7 ± 14.7 years. The prevalence of undernutrition ranged from 3.1% by BMI ≤ 18.5 kg/m² to 75.4% for patients below energy and protein intake recommendations. With the exception of BMI classification, undernourished patients had worse scores in nearly all QoL dimensions (EuroQoL and KDQoL-SF), a pattern which was dominantly maintained when adjusted for demographics and disease-related variables. Overweight/ obese patients (BMI ≥ 25) also had worse scores in some QoL dimensions, but after adjustment the pattern was maintained only in the symptoms and problems dimension of KDQoL-SF (p = 0.011). CONCLUSION Our study reveals that even in mildly undernourished HD patients, nutritional status has a significant impact in several QoL dimensions. The questionnaires used provided different, almost complementary perspectives, yet for daily practice EuroQoL is simpler. Assuring a good nutritional status, may positively influence QoL.
Reconstitution of Peptidoglycan Cross-Linking Leads to Improved Fluorescent Probes of Cell Wall Synthesis

The peptidoglycan precursor, Lipid II, produced in the model Gram-positive bacterium Bacillus subtilis differs from Lipid II found in Gram-negative bacteria such as Escherichia coli by a single amidation on the peptide side chain. How this difference affects the cross-linking activity of penicillin-binding proteins (PBPs) that assemble peptidoglycan in cells has not been investigated because B. subtilis Lipid II was not previously available. Here we report the synthesis of B. subtilis Lipid II and its use by purified B. subtilis PBP1 and E. coli PBP1A. While enzymes from both organisms assembled B. subtilis Lipid II into glycan strands, only the B. subtilis enzyme cross-linked the strands. Furthermore, B. subtilis PBP1 catalyzed the exchange of both d-amino acids and d-amino carboxamides into nascent peptidoglycan, but the E. coli enzyme only exchanged d-amino acids. We exploited these observations to design a fluorescent d-amino carboxamide probe to label B. subtilis PG in vivo and found that this probe labels the cell wall dramatically better than existing reagents.
Barriers to Treatment Engagement for Depression among Latinas

In spite of successful treatment options for depression, the majority of Americans with severe depression do not receive treatment. Latinos are even less likely to engage in treatment than non-Hispanic Whites. The purpose of this study is to explore barriers to treatment engagement and, more specifically, how childhood adversity and gender-based violence (GBV) contribute to a lack of perceived support for treatment engagement. Experiences of GBV and childhood adversity can call into question deeply held family, cultural, and religious values, and affect the perceived quality of the therapeutic relationship and attitudes about depression treatment. A qualitative descriptive methodology was used to understand the experiences of a sample of 12 Latinas who were part of a diabetes prevention study (n = 67) and had been referred for treatment because of elevated symptoms of depression. Results indicate that the often-cited barriers to mental health care (i.e., language barriers, economic considerations, and lack of illness recognition) did not serve as deterrents for Latinas in this study. Participants recognized that they were depressed and agreed with the assessment of depression. However, none of the women followed up on the recommendation to seek care. What has emerged from this study is how cultural values, such as familismo and marianismo, and the lack of responsiveness from family and religious leaders in the context of exposure to GBV and childhood adversity created significant barriers to treatment engagement. This study highlights the need for nurses to screen for these exposures and to engage in shared decision making about treatment.
A Galactic short gamma-ray burst as cause for the 14C peak in AD 774/5

In the last 3000 yr, one significant and rapid increase in the concentration of 14 Ci n tree rings was observed; it corresponds to a γ -ray energy input of 7 × 10 24 erg at Earth within up to one year in AD 774/5. A normal supernova and a solar or stellar flare are unlikely as cause, so that the source remained unknown. Here, we show that a short gamma-ray burst (GRB) in our Galaxy is consistent with all observables: such an event is sufficiently short and provides the necessary energy in the relevant spectral range of γ -rays. Its spectral hardness is consistent with the differential production rates of 14 C and 10 Be as observed. The absence of reports about a historic sighting of a supernova in AD 774/5 or a present-day supernova remnant is also consistent with a short GRB. We estimate the distance towards this short GRB to be ∼1–4 kpc – sufficiently far away, so that no extinction event on Earth was triggered. This is the first evidence for a short GRB in our Galaxy.
Improved seam carving using meta-heuristics algorithms combination

In this paper we propose a novel method to improve seam carving based on the method meta-heuristic algorithms combining simulated annealing (SA) and genetic algorithm (GA). SA is a single solution method which searches locally while GA belongs to population based algorithms that globally search to find the best answer. By this strategy, both speed and quality of the seam carving method can be increased simultaneously. First, SA is performed to find near optimum seams, which form initial population of GA. Then genetic algorithm develops this initial population to find optimum seam. Experimental results show that search for optimum seams by our proposed method successfully improves the retargeting results of seam carving.
Afghanistan's Ethnic Groups Share a Y-Chromosomal Heritage Structured by Historical Events

Afghanistan has held a strategic position throughout history. It has been inhabited since the Paleolithic and later became a crossroad for expanding civilizations and empires. Afghanistan's location, history, and diverse ethnic groups present a unique opportunity to explore how nations and ethnic groups emerged, and how major cultural evolutions and technological developments in human history have influenced modern population structures. In this study we have analyzed, for the first time, the four major ethnic groups in present-day Afghanistan: Hazara, Pashtun, Tajik, and Uzbek, using 52 binary markers and 19 short tandem repeats on the non-recombinant segment of the Y-chromosome. A total of 204 Afghan samples were investigated along with more than 8,500 samples from surrounding populations important to Afghanistan's history through migrations and conquests, including Iranians, Greeks, Indians, Middle Easterners, East Europeans, and East Asians. Our results suggest that all current Afghans largely share a heritage derived from a common unstructured ancestral population that could have emerged during the Neolithic revolution and the formation of the first farming communities. Our results also indicate that inter-Afghan differentiation started during the Bronze Age, probably driven by the formation of the first civilizations in the region. Later migrations and invasions into the region have been assimilated differentially among the ethnic groups, increasing inter-population genetic differences, and giving the Afghans a unique genetic diversity in Central Asia.
The Porter Report Revisited - Creating and assessing a cluster evaluation framework - Application to the Douro region wine cluster

Clusters have been a much diffused concept regarding economic development and national competitiveness. Several countries, governments and policy-makers have used clusters as an economic policy to increase regional competitiveness, however the lack of evaluation has been an issue. In 1994 a report was conducted in Portugal – The Porter Report, in which six industries were deemed relevant by public and private organizations to be part of a cluster initiative. Therefore, and since 20 years have passed from the beginning of this report, and given the fact that Portugal is now facing a lack of competitiveness, it seems suitable to revisit the Porter Report. This dissertation reviews the literature on the topics of competitiveness, geographical and agglomeration economics, clusters and cluster evaluation methods. Secondly, this work provides an overview on the clusters studied by the Porter Report in 1994, which were six: wine, tourism, automobile, footwear, textiles and wood products. The fourth chapter develops a cluster evaluation method, which is applied in the fifth, to the Douro region wine cluster (DRWC), which was deemed as the most relevant to evaluate, due its location and organizational characteristics. The results from seventh chapter show that the DRWC’s location affects positively employment and sales, thus proving the positive effects of clustering. In conclusion, this work aimed at introducing the main literature related with clusters and its evaluation, as well as providing an introductory overview on the main Portuguese industrial clusters and the effect of clusters in the companies’ employment and average sales.
An Econometric Macro-model of Transition: Policy Choices in the Pre-Accession Period

This paper analyses current policy choices facing the candidate countries for EU accession using newly developed econometric macromodels of Poland, Hungary, the Czech Republic, Slovenia and Estonia. The models allow for endogenous growth, and they have been incorporated into an existing global econometric model (NiGEM). This allows long-term projections to be made consistently with expected developments in other economies and allows full feedbacks with the rest of the world so that we can understand impacts on existing EU members as well as the candidate countries. This paper has several novel features, in that we use modern panel data techniques on short time series data in order to construct models of a number of economies. In constructing the models, we have taken special care to consider the roles of openness and foreign investment on productivity and growth. Different policies toward growth and the enhancement of technology transfer are analysed using the models, and policy advice on the accession and integration are made.
RNase E Regulates the Yersinia Type 3 Secretion System

ABSTRACT Yersinia spp. use a type 3 secretion system (T3SS) to directly inject six proteins into macrophages, and any impairment of this process results in a profound reduction in virulence. We previously showed that the exoribonuclease polynucleotide phosphorylase (PNPase) was required for optimal T3SS functioning in Yersinia pseudotuberculosis and Yersinia pestis. Here we report that Y. pseudotuberculosis cells with reduced RNase E activity are likewise impaired in T3SS functioning and that phenotypically they resemble Δpnp cells. RNase E does not affect expression levels of the T3SS substrates but instead, like PNPase, regulates a terminal event in the secretion pathway. This similarity, together with the fact that RNase E and PNPase can be readily copurified from Y. pseudotuberculosis cell extracts, suggests that these two RNases regulate T3SS activity through a common mechanism. This is the first report that RNase E activity impacts the T3SS as well as playing a more general role in infectivity.
Investigation of MicroRNA-21 Expression Levels in Serum and Stool as a Potential Non-Invasive Biomarker for Diagnosis of Colorectal Cancer

Background: Most cancer studies focus on exploring non-invasive biomarkers for cancer detection. In the present study, we sought to investigate the expression level of microRNA-21 (miR-21), as a potential diagnostic marker, in serum and stool samples from 40 patients with colorectal cancer (CRC) and 40 healthy controls. Methods: Quantitative real-time RT-PCR was applied to determine the relative expression level of miR-21 in serum and stool. At the same time, the sensitivity and specificity of this marker was evaluated by receiver operating characteristic (ROC) curve analysis. Results: miR-21 expression levels of serum and stool were up-regulated 12.1 (P<0.05, 95% CI: 5.774-34.045) and 10.0 (P<0.05, 95% CI: 0.351-16.260) times in CRC patients, respectively, when compared to the control group. The sensitivity and specificity of miR-21 was found to be 86.05% and 72.97%, respectively (an area under the ROC curve [AUC] of 0.783). The stool miR-21 level in CRC patients was much higher than that in the healthy controls, showing a sensitivity of 86.05% and a specificity of 81.08% (AUC: 0.829). The expression level of miR-21 in stool was able to significantly distinguish CRC tumor, node, metastasis stages III-IV from stages I-II, with a sensitivity and specificity of 88.1% and 81.6%, respectively (AUC: 0.872). Conclusion: The results of this study indicated that miR-21 expression levels in serum and stool can be considered as a potential diagnostic biomarker for the diagnosis of CRC patients. However, more studies are required to confirm the validity of miR-21 as a valuable non-invasive diagnostic tool for CRC.
Conventional compared with individualized chemotherapy for childhood acute lymphoblastic leukemia.

BACKGROUND The rate of clearance of antileukemic agents differs by a factor of 3 to 10 among children with acute lymphoblastic leukemia. We hypothesized that the outcome of treatment would be improved if doses were individualized to prevent low systemic exposure to the drugs in patients with fast drug clearance. METHODS We stratified and randomly assigned 182 children with newly diagnosed acute lymphoblastic leukemia to postremission regimens that included high-dose methotrexate and teniposide plus cytarabine. The doses of these drugs were based on body-surface area (in the conventional-therapy group) or the rates of clearance of the three medications in each patient (in the individualized-treatment group). In the individualized-treatment group, doses were increased in patients with rapid clearance and decreased in patients with very slow clearance. RESULTS Patients who received individualized doses had significantly fewer courses of treatment with systemic exposures below the target range than did patients who received conventional doses (P<0.001 for each medication). Among the patients with B-lineage leukemia, those who received individualized therapy had a significantly better outcome than those given conventional therapy (P=0.02); the mean (+/-SE) rates of continuous complete remission at five years were 76+/-6 percent and 66+/-7 percent, respectively. There was no significant difference between treatments for patients with T-lineage leukemia (P=0.54). In a proportional-hazards model, the time-dependent systemic exposure to methotrexate, but not to teniposide or cytarabine, was significantly related to the risk of early relapse in children with B-lineage leukemia. CONCLUSIONS Adjusting the dose of methotrexate to account for the patient's ability to clear the drug can improve the outcome in children with B-lineage acute lymphoblastic leukemia.
Methylphenidate for apathy and functional status in dementia of the Alzheimer type.

OBJECTIVE Apathy is the most common behavioral problem in persons with dementia of the Alzheimer type (DAT). Treatment of apathy in DAT is not systematically studied. The purpose of this study was to evaluate the response of apathy to methylphenidate treatment and to examine whether functional status improved. METHODS The authors conducted a 12-week open-labeled study with immediate release formulation of methylphenidate. Twenty-three patients with DAT scoring >40 on the Apathy Evaluation Scale (AES) were recruited. Repeated measures analysis of variance and correlation analysis were performed. RESULTS None of the patients dropped out of the study because of adverse events. Significant improvement in apathy was noted during 12 weeks. Significant improvement was also noted in depression, Mini-Mental State Examination score, and functional status. There was no correlation between changes in the AES and depression scores. CONCLUSIONS Methylphenidate was well tolerated in these patients with DAT. Apathy improved with the use of methylphenidate.
Hylan GF-20 Viscosupplementation in the Treatment of Symptomatic Osteoarthritis of the Knee: Clinical Effect Survivorship at 5 Years

Purpose Controversies remain surrounding the choice of hyaluronic acid products and patient selection. A study was conducted to report the long-term survivorship of intra-articular injection effect of high molecular weight hyaluronic preparation hylan GF-20 (Synvisc-One) for patients with symptomatic knee osteoarthritis. Materials and Methods A retrospective observational analysis of a single therapeutic series was carried out. The analysis was conducted to determine therapeutic effect survivorship taking arthroplasty and any other surgical interventions as endpoint results. Results Seventy-seven consecutive patients (82 knees) were followed up for five years. At one-year follow-up, 71 knees (87%) responded to treatment and only 8 knees (10%) were offered arthroplasty due to persistence of symptoms. At five-year follow-up, 41 (50%) were still considered responders. During the study period, repeat injection was given in 9 knees (11%). Arthroplasty (either total or unicompartmental) was required in 26 (31%). Kaplan-Meier survivorship analysis of therapeutic effect demonstrated 67% survival at 5 years with arthroplasty as endpoint and 58% survival at 5 years with all secondary interventions as endpoint. Conclusions This study demonstrates a significantly longer duration of clinical benefit of hylan GF-20 injection. Present results may suggest a notion of an ideal delay therapeutic strategy for patients not ready to receive an arthroplasty. Further studies will be required to help characterise these subsets of patients.