Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysing microarray data in drug discovery using systems biology

The innovation of present drug design focuses on new targets. However, compound efficacy and safety in human metabolism, including toxicity and pharmacokinetic profiles, but not target selection, are the criteria that determine which drug candidates enter the clinic. Systems biology approaches to disease are developed from the idea that disease-perturbed regulatory networks differ from their normal counterparts. Microarray data analyses reveal global changes in gene or protein expression in response to genetic and environmental changes and, accordingly, are well suited to construct the normal, disease-perturbed and drug-affected networks, which are useful for drug discovery in the pharmaceutical industry. The integration of modelling, microarray data and systems biology approaches will allow for a true breakthrough in in silico absorption, distribution, metabolism, excretion and toxicity assessment in drug design. Therefore, drug discovery through systems biology by means of microarray analyses could significantly reduce the time and cost of new drug development.
Wireless DF Relaying with Beamforming for an Unmanned Aircraft System over κ-μ Fading Channels

In this paper, we propose a dual-hop decode-and-forward (DF) relaying network with beamforming for an unmanned aircraft system (UAS) over ? fading channels. The ? –? fading model is a general fading model that models wireless fading channel perfectly in line-of-sight (LOS) propagation environments and includes Nakagami-m, Rician, Rayleigh, and One-sided Gaussian fading channels as special cases. We consider an unmanned aerial vehicle (UAV) as a moving relay for forwarding the data signals from a source ground station (GS) to a destination GS. Our proposed system considers multiple antennas at the source and destination, whereas the relay has a single antenna. We derive a closed-form expression for the outage probability in terms of the generalized Marcum Q-function. We carry out the performance analysis by means of derived expression for the various antenna arrangements, distinct values of radius, and different values of fading parameters. Our results show that the number of antennas and fading parameters, ? and ? , have a positive relation with system performance. The analytical results are validated through Monte Carlo simulations.
Cytochrome P450cin (CYP176A), Isolation, Expression, and Characterization*

Cytochromes P450 are members of a superfamily of hemoproteins involved in the oxidative metabolism of various physiologic and xenobiotic compounds in eukaryotes and prokaryotes. Studies on bacterial P450s, particularly those involved in monoterpene oxidation, have provided an integral contribution to our understanding of these proteins, away from the problems encountered with eukaryotic forms. We report here a novel cytochrome P450 (P450cin, CYP176A1) purified from a strain ofCitrobacter braakii that is capable of using cineole 1 as its sole source of carbon and energy. This enzyme has been purified to homogeneity and the amino acid sequences of three tryptic peptides determined. By using this information, a PCR-based cloning strategy was developed that allowed the isolation of a 4-kb DNA fragment containing the cytochrome P450cin gene (cinA). Sequencing revealed three open reading frames that were identified on the basis of sequence homology as a cytochrome P450, an NADPH-dependent flavodoxin/ferrodoxin reductase, and a flavodoxin. This arrangement suggests that P450cin may be the first isolated P450 to use a flavodoxin as its natural redox partner. Sequencing also identified the unprecedented substitution of a highly conserved, catalytically important active site threonine with an asparagine residue. The P450 gene was subcloned and heterologously expressed in Escherichia coli at ∼2000 nmol/liter of original culture, and purification was achieved by standard protocols. Postulating the native E. coli flavodoxin/flavodoxin reductase system might mimic the natural redox partners of P450cin, it was expressed inE. coli in the presence of cineole 1. A product was formedin vivo that was tentatively identified by gas chromatography-mass spectrometry as 2-hydroxycineole 2. Examination of P450cin by UV-visible spectroscopy revealed typical spectra characteristic of P450s, a high affinity for cineole 1 (K D = 0.7 μm), and a large spin state change of the heme iron associated with binding of cineole 1. These facts support the hypothesis that cineole 1 is the natural substrate for this enzyme and that P450cin catalyzes the initial monooxygenation of cineole 1 biodegradation. This constitutes the first characterization of an enzyme involved in this pathway.
Semi-Supervised Active Clustering with Weak Oracles

Semi-supervised active clustering (SSAC) utilizes the knowledge of a domain expert to cluster data points by interactively making pairwise "same-cluster" queries. However, it is impractical to ask human oracles to answer every pairwise query. In this paper, we study the influence of allowing "not-sure" answers from a weak oracle and propose algorithms to efficiently handle uncertainties. Different types of model assumptions are analyzed to cover realistic scenarios of oracle abstraction. In the first model, random-weak oracle, an oracle randomly abstains with a certain probability. We also proposed two distance-weak oracle models which simulate the case of getting confused based on the distance between two points in a pairwise query. For each weak oracle model, we show that a small query complexity is adequate for the effective $k$ means clustering with high probability. Sufficient conditions for the guarantee include a $\gamma$-margin property of the data, and an existence of a point close to each cluster center. Furthermore, we provide a sample complexity with a reduced effect of the cluster's margin and only a logarithmic dependency on the data dimension. Our results allow significantly less number of same-cluster queries if the margin of the clusters is tight, i.e. $\gamma \approx 1$. Experimental results on synthetic data show the effective performance of our approach in overcoming uncertainties.
The cell-mediated immune response to Borrelia afzelii, garinii and burgdorferi in C57BL/6 mice is dependent on antigen specificity.

Inbred C57BL/6 mice were challenged with Borrelia afzelii, Borrelia garinii and Borrelia burgdorferi sensu stricto and tested for antigen-specific T-cell response in vitro. The sonicated preparations of in vitro grown spirochetes were capable of stimulating polyclonal proliferation and specific cell-mediated response, depending on duration of the cell culture. Murine splenocytes previously sensitized to B. burgdorferi sensu lato (s.l. ), but not those from control mice, could be induced for antigen-specific proliferation in vitro. Moreover, detectable cell-mediated response could be induced only with antigen preparations derived from a corresponding strain but not with those obtained from other Borrelia genospecies as revealed by the [(3)H]thymidine incorporation assay. The current study considers that the strict B. burgdorferi s.l. antigen-specific response may also be expected in infections in humans and contributes to the explanation of the frequently poor antibody- and cell-mediated immune response observed in patients diagnosed with Lyme disease.
Interactions of Interleukin‐6 Promoter Polymorphisms With Dietary and Lifestyle Factors and Their Association With Bone Mass in Men and Women From the Framingham Osteoporosis Study

Lifestyle and dietary factors may influence the association of IL‐6 polymorphisms with bone mass. In 1574 unrelated men and women from the Framingham Offspring Cohort, we observed significant hip BMD differences between IL‐6 −174 genotypes only in older women, those without estrogens, and those with a poor calcium intake. Hence, association of IL‐6 polymorphisms with BMD may be limited to discrete population subgroups.
Optimal code rate for wireless sensor networks using IR-UWB and non-coherent detection

In this paper, a cross-layer design approach has been used to evaluate the effect of forward error correction (FEC) on energy consumption of non-coherent energy detector receiver using impulse radio ultra-wideband in the context of wireless sensor networks. The proposed method captures relevant characteristics of the physical and medium access control (MAC) layers, while taking into account bit error probability (BEP) requirement of the application. A two-stage semi-analytical optimization model and code rate selection algorithm has been developed to find out the optimal code rate from the energy efficiency perspective. Firstly, a signal-to-noise ratio (SNR) gap analysis is used to select the code rates, which can provide the same target BEP as uncoded transmission, with lower received SNR. Secondly, an energy consumption model is used to explore which one of the selected code rates provide the highest energy saving, when compared to the uncoded case. In this work, the proposed algorithm has been executed for Reed-Solomon codes using Nakagami-m fading channel model and taking into account the channel access success probability of the Slotted Aloha MAC for different offered traffic loads. The results clearly illustrate the potential energy savings that can be achieved by using FEC and selecting the optimum code rate. The developed model is useful in the selection of code rate for particular communication distances and offered traffic load values.
Adult abdominal migraine: a new syndrome or sporadic feature of migraine headache? A case report

Abdominal migraine is one of the variants of migraine headache typically occurring in children and coded as 1.3. 2 in the revised edition of IHS classification within the group ‘Childhood periodic syndromes that are commonly precursors of migraine’. The affected children frequently develop typical migraine later in their life. We report a case of a 23 years old woman affected by attacks of recurrent abdominal pain accompanied by migraine. Abdominal pain attacks started in the adolescence and persisted without headache until the patient was 21. At this time, she experienced migraine pain accompanied by nausea, photophobia and phonophobia and associated to acute abdominal pain. Neuroimaging investigations and laboratory testing excluded any underlying organic disease. Complete remission of abdominal attacks was obtained during 4‐month treatment period with pizotifen. Attacks fulfil IHS diagnostic criteria for ‘abdominal migraine’, although of late onset. This case report suggests that ‘abdominal migraine’ is a migraineous disorder to be hypothesized in adult patients after having disclosed any organic disease. As reported in the literature, ‘adult abdominal migraine’ is a sporadic migraine subtype in adult patients and it is not to be considered as a new migraineous syndrome.
Building Better Caregivers: A Pragmatic 12-Month Trial of a Community-Based Workshop for Caregivers of Cognitively Impaired Adults

Building Better Caregivers (BBC), a community 6-week, peer-led intervention, targets family caregivers of those with cognitive impairments. BBC was implemented in four geographically scattered areas. Self-report data were collected at baseline, 6 months, and 1 year. Primary outcome were caregiver strain and depression. Secondary outcomes included caregiver burden, stress, fatigue, pain, sleep, self-rated health, exercise, self-efficacy, and caregiver and care partner health care utilization. Paired t tests examined 6 month and 1-year improvements. General linear models examined associations between baseline and 6-month changes in self-efficacy and 12-month primary outcomes. Eighty-three participants (75% of eligible) completed 12-month data. Caregiver strain and depression improved significantly (Effect Sizes = .30 and .41). All secondary outcomes except exercise and caregiver health care utilization improved significantly. Baseline and 6-month improvements in self-efficacy were associated with improvements in caregiver strain and depression. In this pilot pragmatic study, BBC appears to assist caregivers while reducing care partner health care utilization. Self-efficacy appears to moderate these outcomes.
Impairment of hippocampal gamma (γ)‐frequency oscillations in vitro in mice overexpressing human amyloid precursor protein (APP)

Alzheimer's disease is associated with a dramatic decline in cognitive performance including hippocampal‐dependent memory. We have investigated one feature of hippocampal activity related to memory, the γ (30–80 Hz)‐frequency rhythm. Hippocampal slices from mice overexpressing the human amyloid precursor protein (APP)SWE mutation (TAS10) were compared at 8 and 16 months of age with wild‐type littermates. In slices obtained from TAS10 mice aged 8 months the γ‐frequency activity evoked with bath application of 200 nm kainate was significantly (P < 0.05; n = 8 slices, five animals) impaired (area power, 5956 ± 2487 µV2) compared to slices from wild‐type animals (area power, 18 256 ± 7880 µV2). At 16 months of age there was no longer a significant difference (P > 0.05; n = 11 slices from five animals) between slices from TAS10 and wild‐type control mice as the wild‐type mice now exhibited a marked age‐dependent reduction in γ‐frequency activity (TAS10 area power, 5751 ± 1573 µV2; wild‐type area power = 5379 ± 1454 µV2). Although no dense‐core plaques were evident at 8 months there was detectable amyloid labelling in the TAS10 mice which might account for the deficits in γ activity observed at this age. Dense plaques were clearly evident in the TAS10, but not wild‐type, mice at 16 months of age but no further reductions in γ‐frequency activity were seen in the TAS10 mice. These data suggest that deficits in network function in Alzheimer's disease occur early and are not directly correlated to amyloid load.
Etiological heterogeneity of symptom dimensions of adolescent depression.

The aim was to investigate the underlying factor structure of adolescent depression and etiological heterogeneity in the symptom dimensions of adolescent depression. The sample included 842 pairs of same-sex adolescent twins, among which 613 pairs were monozygotic twins and 229 pairs were dizygotic twins. The ages of the participants ranged from 11 to 17 years (M = 13.64, SD = 1.80). Adolescents' depressive symptoms were assessed using the self-reported Children's Depression Inventory. Exploratory and confirmatory factor analyses were used to explore the factor structure of youth depression and twin genetic analyses were employed to estimate genetic and environmental influences on the derived dimensions. Results showed that adolescent depression encompassed five correlated dimensions: dysphoria mood, somatic symptoms, study and externalizing problems, anhedonia symptoms, and cognitive symptoms. These five symptom dimensions had heterogeneous etiologies: Dysphoria mood, somatic symptoms, and cognitive symptoms were moderately heritable (heritability ranged from 33 to 40%), whereas study and externalizing problems, and anhedonia symptoms were mainly environmentally influenced with minimal genetic basis. Our findings supported the multidimensionality of adolescent depression and the etiological heterogeneity of these symptom dimensions.
Prevalence of risk factors of ST segment elevation myocardial infarction in Turkish patients living in Central Anatolia.

OBJECTIVE There is not enough available data in our country about the prevalence of risk factors for ST-elevation myocardial infarction (STEMI), which has the highest in-hospital mortality rate within subtypes of acute coronary syndromes. Therefore, in this study, we aimed to evaluate the prevalence of risk factors for STEMI in Central Anatolia, one of the regions with high risk for coronary heart disease (CHD). METHODS This cross-sectional observational study included 1210 patients (962 men, 248 women) with the diagnosis of STEMI in 3 tertiary-medical centers in 3 cities in Central-Anatolia (Ankara, Konya, and Kayseri). Demographic characteristics (age, gender) and risk factors known to be traditional risk factors for CHD (history of hypertension (HT), diabetes mellitus (DM), smoking, and family history) were inquired and fasting blood samples within 24 hours from onset of STEMI were taken to analyze lipid levels. Patients were divided into 3 groups based on their ages: Group A--age = or <44 years; Group B--age 45-64 years; and Group C--age = or >65 years. Prevalence of risk factors and differences within age-groups and genders were evaluated. RESULTS The mean age was 58+/- 11 years (range 24-96 years). Although the percentage of female patients increased in relation to increasing age, 80% of the total patients were male. While prevalence of smoking and family history was observed to decrease with aging, there was a statistically significant increase in prevalence of HT and DM (p<0.001). Prevalence of smoking was the highest in young patients and males (p<0.001). Prevalence of HT and DM, on the other hand, was significantly higher in women than in men (p<0.001). Although the number of modifiable risk factors was found to be significantly smaller in men, male patients with STEMI were 8 years younger than females on average. CONCLUSIONS The results of our study, in which modifiable risk factors and especially smoking were found to have a high prevalence in patients with STEMI living in Central Anatolia, suggested that most STEMI cases especially at younger ages might be prevented by the modification of these risk factors.
3-Hydroxy-3-methylglutaryl-coenzyme A reductase from Haloferax volcanii: purification, characterization, and expression in Escherichia coli

Prior work from this laboratory characterized eukaryotic (hamster) and eubacterial (Pseudomonas mevalonii) 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductases. We report here the characterization of an HMG-CoA reductase from the third domain, the archaea. HMG-CoA reductase of the halobacterium Haloferax volcanii was initially partially purified from extracts of H. volcanii. Subsequently, a portion of the H. volcanii lovastatin (formerly called mevinolin) resistance marker mev was subcloned into the Escherichia coli expression vector pT7-7. While no HMG-CoA reductase activity was detectable following expression in E. coli, activity could be recovered after extracts were exposed to 3 M KCl. Following purification to electrophoretic homogeneity, the specific activity of the expressed enzyme, 24 microU/mg, equaled that of homogeneous hamster or P. mevalonii HMG-CoA reductase. Activity was optimal at pH 7.3. Kms were 66 microM (NADPH) and 60 microM [(S)-HMG-CoA]. (R)-HMG-CoA and lovastatin inhibited competitively with (S)-HMG-CoA. H. volcanii HMG-CoA reductase also catalyzed the reduction of mevaldehyde [optimal activity at pH 6.0; Vmax 11 microU/mg; Kms 32 microM (NADPH), 550 microM [(R,S)-mevaldehyde]] and the oxidative acylation of mevaldehyde [optimal activity at pH 8.0; Vmax 2.1 microU/mg; Kms 350 microM (NADP+), 300 microM (CoA), 470 microM [(R,S)-mevaldehyde]]. These properties are comparable to those of hamster and P. mevalonii HMG-CoA reductases, suggesting a similar catalytic mechanism.
LMI-Based Stability Criteria With Auxiliary Matrices for Delayed Recurrent Neural Networks

In this note, the global asymptotic stability for delayed recurrent neural networks is addressed with a new Lyapunov-Krasovskii function. New delay-independent linear matrix inequality (LMI)-based conditions for global asymptotic stability are derived. A key feature of the new approach is the introduction auxiliary matrices, which can provide useful and less conservative results. This feature also enables us to cast a series of previous LMI-based results into even more general framework, logic flow of ideas and comparisons are thus easily shown. Three numerical examples show the effectiveness of the proposed method.
Reversal of sedation and respiratory depression after anaesthesia by the combined use of physostigmine and naloxone in neurosurgical patients

A clinical trial of the combination of naloxone in alow dose (1–1.5 μg·kg‐1 body weight) with physostigmine (0.5–1.0 mg i.v.) was made to elucidate whether this combination could reverse postanaesthetic oversedation in neurosurgical patients without increasing postoperative pain. The investigation was made following previous findings that physostigmine has analgesic properties in addition to its systemic antisedative and anticholinergic effects as well as a stimulatory effect on morphine‐depressed ventilation. Altogether 198 neurosurgical patients were investigated. The results showed that postanaesthetic oversedation can be safely treated by a combination of naloxone and physostigmine in the dosages named above, resulting in the rapid reversal of sedation, where opiates, neuroleptics and benzodiazepines have been used. In contrast, this combination has very little effect on sedation following the administration of agents such as halothane and isoflurane. In the great majority of patients (95%), the treatment resulted in excellent analgesia during the first postoperative hour. The incidence of nausea and vomiting was increased somewhat by this treatment, but these side‐effects could be minimized by decreasing the rate of drug administration. Physostigmine is contra‐indicated in patients having symptoms and signs similar to those of Parkinson's disease, and the dose of physostigmine should also be reduced to 0.5 mg i.v. in all patients over the age of 65.
Highlights from the history of sexual medicine.

INTRODUCTION Today, we have a clear concept of sexual medicine and how to define this medical discipline. But historically, the unification of sexuality and medicine was not a given condition. Medicine was mainly focused on human reproduction and how to prevent and treat sexually transmitted diseases. Hardly any other aspect would have met the interest of medical doctors for centuries. METHODS Historical review that can only highlight developments and milestones of sexual medicine and is not intended to be encyclopedic. RESULTS Perhaps, the first true medicalization of sexuality was the dreadful anti-masturbation campaign led by doctors, beginning with Tissot, since the middle of the 18th century. In the 2nd half of the 19th century, first pioneers like the physician Paolo Mantagazza were systematically addressing issues related to human sexuality. This highly developing scientific field and medical community were destroyed after 1933 by the political influence of the national socialists in Europe. After World War II, a new era started with the works of Alfred Kinsey and other sexologists mainly in the United States of America. CONCLUSIONS The term sexual medicine was established around 1970, most likely in Europe, and subsequently resulted in a new worldwide academic and clinical speciality.