Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic hydrogen bonding and DNA flexibility in minor groove binders: molecular dynamics simulation of the polyamide f‐ImPyIm bound to the Mlu1 (MCB) sequence 5′‐ACGCGT‐3′ in 2:1 motif

Molecular dynamics simulations of the DNA 10‐mer 5′‐CCACGCGTGG‐3′ alone and complexed with the formamido‐imidazole‐pyrrole‐imidazole (f‐ImPyIm) polyamide minor groove binder in a 2:1 fashion were conducted for 50 ns using the pbsc0 parameters within the AMBER 12 software package. The change in DNA structure upon binding of f‐ImPyIm was evaluated via minor groove width and depth, base pair parameters of Slide, Twist, Roll, Stretch, Stagger, Opening, Propeller, and x‐displacement, dihedral angle distributions of ζ, ε, α, and γ determined using the Curves+ software program, and hydrogen bond formation. The dynamic hydrogen bonding between the f‐ImPyIm and its cognate DNA sequence was compared to the static image used to predict sequence recognition by polyamide minor groove binders. Many of the predicted hydrogen bonds were present in less than 50% of the simulation; however, persistent hydrogen bonds between G5/15 and the formamido group of f‐ImPyIm were observed. It was determined that the DNA is wider in the Complex than without the polyamide binder; however, there is flexibility in this particular sequence, even in the presence of the f‐ImPyIm as evidenced by the range of minor groove widths the DNA exhibits and the dynamics of the hydrogen bonding that binds the two f‐ImPyIm ions to the minor groove. The Complex consisting of the DNA and the 2 f‐ImPyIm binders shows slight fraying of the 5′ end of the 10‐mer at the end of the simulation, but the portion of the oligomer responsible for recognition and binding is stable throughout the simulation. Several structural changes in the Complex indicate that minor groove binders may have a more active role in inhibiting transcription than just preventing binding of important transcription factors. Copyright © 2015 John Wiley & Sons, Ltd.
Costo del tratamiento farmacológico de las reacciones adversas graves por medicamentos en Cuba (2003-2013)

RESUMEN Introduccion: Los problemas de seguridad y costo de las reacciones adversas medicamentosas (RAM) graves tienen un peso considerable en los sistemas de salud, pero la evidencia demostrada en los estudios publicados en Cuba, es aun escasa. Objetivo: Determinar costos asociados al tratamiento farmacologico de las reacciones adversas graves en el pais. Metodo: Se realizo una evaluacion parcial de tipo descripcion de costos desde la perspectiva del Sistema Nacional de Salud en el periodo 2003-2013. Se utilizo una tecnica de microcosteo, se calcularon los costos unitarios y totales para un horizonte temporal de 24 horas de ocurrida la reaccion adversa grave y estos se expresaron en pesos cubanos. Resultados: Del total de RAM graves, en 13 293 hubo descripcion del tratamiento farmacologico inmediato (17,9 %). Este represento un costo total de $ 62 228,05. El costo medio fue de $ 4,69. Los mayores porcentajes de RAM graves se ubicaron en los rangos entre $ 1,00 y 3,00 (24,3 %). Se observo que las RAM de hipersensibilidad representaron el 34,2 % del costo total con $ 21 283,41 CUP. Aquellas de intensidad moderada representaron el 81,7 % de los costos. Practicamente en todos los casos costo mas tratar las RAM graves que el costo del tratamiento farmacologico que la origino. Conclusiones: Los resultados muestran que las RAM graves verifican un problema y generan un costo para el sistema nacional de salud, por lo que se requieren medidas encaminadas a su deteccion y prevencion para mejorar la seguridad del paciente y reducir los costos.
Improved Physical Performance in Older Adults Undertaking a Short-Term Programme of High-Velocity Resistance Training

Background: The age-related loss of muscle power in older adults is greater than that of muscle strength and is associated with a decline in physical performance. Objective: To investigate the effects of a short-term high-velocity varied resistance training programme on physical performance in healthy community-dwelling adults aged 60–80 years. Methods: Subjects undertook exercise (EX; n = 15) or maintained customary activity (controls, CON; n = 10) for 8 weeks. The EX group trained 2 days/week using machine weights for three sets of eight repetitions at 35, 55, and 75% of their one-repetition maximum (the maximal weight that an individual can lift once with acceptable form) for seven upper- and lower-body exercises using explosive concentric movements. Results: Fourteen EX and 10 CON subjects completed the study. Dynamic muscle strength significantly increased (p = 0.001) in the EX group for all exercises (from 21.4 ± 9.6 to 82.0 ± 59.2%, mean ± SD) following training, as did knee extension power (p < 0.01). Significant improvement occurred for the EX group in the floor rise to standing (10.4 ± 11.5%, p = 0.004), usual 6-metre walk (6.6 ± 8.2%, p = 0.010), repeated chair rise (10.4 ± 15.6%, p = 0.013), and lift and reach (25.6 ± 12.1%, p = 0.002) performance tasks but not in the CON group. Conclusions: Progressive resistance training that incorporates rapid rate-of-force development movements may be safely undertaken in healthy older adults and results in significant gains in muscle strength, muscle power, and physical performance. Such improvements could prolong functional independence and improve the quality of life.
Ease of Attribution, Ease of Licensing, and Integration of Creative Works

Integration is the most fruitful phase of the creative process. Integration occurs when an individual synthesizes some or all components of other individuals' creative works into a new whole which is distinct from the original creative works. Because an integrative creative product uses previously produced works, legal and intellectual property aspects of integrative outcome impact an individual's tendency to engage in the integration process. Concerns over attribution and licensing of creative works can hinder the creative integration process. Intellectual property protection frameworks such as Creative Commons (CC) and technological features such as attribution tree eliminate part of attribution and licensing concerns and thus foster creative integration. In this paper we present a theoretical model and research design for examining impacts of ease of attribution and licensing on creative integration. To inform empirical design, we perform and report an explorative data analysis of creative integration activities in ccMixter which is a CC-based music community.
National Trends in Condom Use Among At‐Risk Heterosexuals in the United States

Based on national level surveys, we examined data relevant to the United States' overall effort to prevent the spread of HIV among heterosexual adults. We examined changes in condom use among at‐risk heterosexuals over the past decade. The observed increases over time in condom use across all heterosexual at‐risk population segments are consistent with the observed (declines) trends in HIV and syphilis in the 1990s. These results and findings from prior studies suggest that U.S. efforts to facilitate condom use and contain HIV and related sexually transmitted disease (STD)cofactors among adult at risk heterosexuals was succeeding over most of the 1990s. The absence of national level behavioral trend data after 1996, and the ambiguities of HIV spread suggest some caution in projecting trends into this century. National and local efforts need to be directed at sustaining behavioral change and conducting more rigorous studies on population trends in HIV/STD‐related behaviors/pathogens.
Protease‐activated receptor‐induced Akt activation – regulation and possible function

Summary. Background: Thrombin induces the activation of the platelet serine/threonine kinase Akt. Akt activation is dependent on its phosphorylation at Thr308 and Ser473. The mechanism by which thrombin induces Akt phosphorylation is controversial, as is the role of Akt in platelet function. Objectives: To investigate how protease‐activated receptors (PARs) stimulate Akt and the role that Akt plays in human platelet function. Methods: Platelets were stimulated through PAR1 or PAR4. Specific inhibitors were used to evaluate, by Western blotting, signaling pathways regulating Akt phosphorylation, and the role of activated Akt was evaluated by aggregometry and flow cytometry. Results: Phospholipase C (PLC) controls Akt phosphorylation elicited by PARs. Stimulation of PAR1 or PAR4 resulted in rapid Akt phosphorylation, independently of secreted ADP and phosphatidylinositol‐3‐kinase (PI3K) activation. Akt phosphorylation ∼60 s after PAR1 stimulation became entirely dependent on the purinergic receptor P2Y12 and the activation of PI3K. In contrast, PAR4 partially sustained Akt phosphorylation independently of P2Y12 and PI3K for up to 300 s. Pharmacologic inhibition of Akt reduced P‐selectin expression and fibrinogen binding in platelets stimulated through PAR1, and delayed platelet aggregation in response to submaximal PAR1 or PAR4 stimulation, although aggregation at 300 s was unaffected. Conclusions: Platelet PAR stimulation causes rapid Akt phosphorylation downstream of PLC, whereas with continuous stimulation, ADP and PI3K are required for maintaining Akt phosphorylation. Activated Akt regulates platelet function by modulating secretion and αIIbβ3 activation.
Laboratory culture and evaluation of the tubeworm Ficopomatus enigmaticus for biofouling studies

Ficopomatus enigmaticus, a euryhaline tube-building polychaete worm with a subtropical to temperate distribution, is an increasingly problematic fouling organism. In this study, laboratory protocols for maintaining adult broodstock, destructive spawning, larval culture and a settlement bioassay were developed. The method routinely yielded approximately 200 larvae per spawning adult. The mean number of eggs released by females was 1517 and the mean number of spermatozoids per male was 4.425 × 106. Fertilisation success, using an initial concentration of 2.5 × 106 spermatozoids and 45 eggs ml−1, was 76% after a contact time of 60 min. The first cleavage occurred after 20 min and the trocophore larval stage was attained by 18 h. Metatrochophores were observed 4 d post-fertilisation and were competent to settle 1 day later. The proportion of larvae that settled after 48 h was surface-dependent: 10.24% on glass, 1.39% on polystyrene and 11.07% on a poly(dimethylsiloxane) elastomer. The presence of a biofilm on glass increased the rate of settlement 7-fold compared to clean glass.
Experimental Verification of PER Performance of STBC-Based Multi-Hop Cooperative Relaying

In this paper, the end-to-end packet error rate (PER) performance of a space-time block code (STBC) based multi-hop cooperative relaying system is discussed. This system consists of a source, a destination, and two STBC based cooperative relays in each hop. These relays decode their received packets and forward the packets only when no error is found. In this system, there are conditions where the end-to-end PER performance improves with the number of hops. The theoretical end-to-end PER performance of this system have been derived analytically. However, in real-world wireless systems, various practical issues, e.g., timing synchronization and imperfect channel estimation, have a large impact on the performance. To confirm the end-to-end PER performance of this system in actual setup, an in-lab experiment using a fading emulator and four transceivers is performed under Rayleigh fading environment. The experimental results clarify the PER performance of the STBC based multi-hop cooperative relaying system. In addition, the theoretical PER performance is also verified from the experimental results.
Research of Fire Detecting System Based on ZigBee Wireless Network

This paper puts forward a strategy of intellectualized fire monitor based on ZigBee transmission. In this system, a low power, multi-parameter composite fire detection node is used, which can detect temperature, smoke concentration and CO gas concentration. The hardware and software implementation are based on 2.4GHz wireless communication chip CC2430. ZigBee protocol is adopted in the system to form reliable wireless communication. The system uses fusion theory to handle the data in order to determine whether the fire occurs.
Pressure-induced high-spin to low-spin transition in CaFeO3.

In situ 57 Fe Mossbauer spectroscopy and x-ray diffraction on CaFeO 3 (Fe 4+ :t 3 2e 1 ) under pressure have revealed a first-order high-spin (S=2) to low-spin (S=1) transition near 30 GPa. The spin and structure transition is an alternative manifestation of the electronic instabilities of the σ-bonding Fe-O-Fe orbitals; at atmospheric pressure a second-order disproportionation 2Fe 4+ ↔Fe 4-δ +Fe 4+δ , 0≤δ ≤1, occurs at a T t ≃290 K
Stress response of rats to handling and experimental procedures

The effects were observed of moving male, adult Han:Sprague rats in their cages or of exposure to ether for 1 min on the plasma concentration profiles of 25 blood characteristics linked with stress and shock reactions. 5 min after the stress serum prolactin, corticosterone, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, triiodothyronine and thyroxin levels were elevated 150-500% compared with those in blood collected within 100 s of entering the animal room. Heart rate (telemetrically recorded), packed cell volume,, haemoglobin and plasma protein content were 10-20% elevated 2-10 min after cage movement or 2-20 min after ether confrontation over those of controls sampled within 50 s, indicating circulatory and microcirculatory shock reactions. Serum glucose, pyruvate and lactate concentrations rose by 20-100% 1-5 min after cage movement and 1-15 min after ether exposure. Phosphate, calcium, urea, apartate and alanine transferases, alkaline phosphalase and leucine arylamidase were not altered significantly by either stressor, while potassium and bound glycerol fell for 1 min and 5-20 min respectively. The presence of a familiar animal attendant working in the room without touching the cages did not markedly affect the blood characteristics being studied.
Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer.

PURPOSE The primary objective of this phase I trial was to determine the maximum-tolerated dose of radiation that could be delivered to the primary tumor concurrent with full-dose gemcitabine in patients with advanced pancreatic cancer. PATIENTS AND METHODS Thirty seven patients with unresectable (n = 34) or incompletely resected pancreatic cancer (n = 3) were treated. Gemcitabine was administered as a 30-minute intravenous infusion at a dose of 1,000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. Radiation therapy was initiated on day 1 and directed at the primary tumor alone, without prophylactic nodal coverage. The starting radiation dose was 24 Gy in 1.6-Gy fractions. Escalation was achieved by increasing the fraction size in increments of 0.2 Gy, keeping the duration of radiation constant at 3 weeks. A second cycle of gemcitabine alone was intended after a 1-week rest. RESULTS Two of six assessable patients experienced dose-limiting toxicity at the final planned dose level of the trial (42 Gy in 2.8-Gy fractions), one with grade 4 vomiting and one with gastric/duodenal ulceration. Two additional patients at this dose level experienced late gastrointestinal toxicity that required surgical management. CONCLUSION The final dose investigated (42 Gy) is not recommended for further study considering the occurrence of both acute and late toxicity. However, a phase II trial of this novel gemcitabine-based chemoradiotherapy approach, at a radiation dose of 36 Gy in 2.4-Gy fractions, is recommended on the basis of tolerance, patterns of failure, and survival data.
Role for the Fission Yeast RecQ Helicase in DNA Repair in G2

ABSTRACT Members of the RecQ helicase subfamily are mutated in several human genomic instability syndromes, such as Bloom, Werner, and Rothmund-Thomson syndromes. We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3′-to-5′ helicase and exists with Top3 in a high-molecular-weight complex. top3 deletion is inviable, and this is suppressed by concomitant loss of rqh1 helicase activity or loss of recombination functions. This is consistent with RecQ helicases in other systems. By using epistasis analysis of the UV radiation sensitivity and by analyzing the kinetics of Rhp51 (Rad51 homologue), Rqh1, and Top3 focus formation in response to UV in synchronized cells, we identify the first evidence of a function for Rqh1 and Top3 in the repair of UV-induced DNA damage in G2. Our data provide evidence that Rqh1 functions after Rad51 focus formation during DNA repair. We also identify a function for Rqh1 upstream of recombination in an Rhp18-dependent (Rad18 homologue) pathway. The model that these data allow us to propose helps to reconcile different interpretations of RecQ family helicase function that have arisen between work based on the S. pombe system and models based on studies of Saccharomyces cerevisiae SGS1 suggesting that RecQ helicases act before Rad51.
Increased plasma prolactin levels in ovariectomized thyroidectomized rats treated with estrogen.

It is well established that TRH exerts a stimulatory effect on the secretion of both TSH and PRL. Clinically, hyperprolactinemia is usually present in hypothyroid women, but not men. In experimental studies, results vary because of the sexes, and treatments of animals differ. The purpose of this study was to further investigate the physiological control of PRL secretion in hypothyroid female rats. Adult female Sprague-Dawley rats that were surgically ovariectomized (OVX) and/or thyroidectomized (Tx) for 2 weeks were used. Serial blood samples were collected through indwelling intraatrial catheters, and plasma PRL and TSH levels were measured by RIA. We found that OVX + Tx and polyestradiol phosphate (PEP; 0.1 mg/rat, sc)-treated rats exhibited significantly higher basal PRL and TSH levels and afternoon surge PRL levels than sham Tx rats with the same treatments. On the other hand, if OVX + Tx rats were not treated with estrogen, their plasma PRL levels were not significantly different from those in sham Tx controls. If challenged with TRH (1 microgram/rat, iv), significantly higher PRL responses were found in OVX + Tx + PEP rats than in sham Tx rats. The contents of TRH in the median eminence of Tx rats, however, were not different from those in sham Tx rats. When challenged with domperidone (10 micrograms/rat, iv), a dopamine antagonist, no difference in PRL increments was found in the two groups of animals. Treatment with CB154, a potent dopamine agonist, did not eliminate the difference in basal PRL levels between the two groups. Pretreatment with a smaller dose of domperidone (1 microgram/rat), however, enhanced the PRL-releasing effect of TRH more in Tx than in sham Tx rats. When T4 (2 or 10 micrograms/100 g BW.day for 21 days) was replaced in Tx rats starting the second day after Tx, both basal and TRH-stimulated PRL secretion were significantly decreased in a dose-dependent manner. In conclusion, the increased PRL levels in OVX + Tx + PEP rats may be due to increased responsiveness of the anterior pituitary gland to TRH, and not to a decreased responsiveness to dopamine. In addition, the elevation of plasma PRL in OVX + Tx + PEP rats is negatively correlated with plasma levels of thyroid hormone.
The somatosensory blink reflex in upper and lower brainstem lesions

The brainstem pathways that mediate the somatosensory blink reflex (SBR) are not completely understood. We hypothesized that the circuits of the SBR might be affected separately from those of the trigeminal blink reflex (TBR). We examined 7 patients with mesencephalic lesions and 8 patients with medullary lesions. The SBR was elicited by median nerve stimulation. The TBR was elicited by supraorbital nerve stimulation. In patients with upper brainstem lesions, the TBR was normal, whereas the SBR was generally abnormal. The SBR was either absent or small and was significantly delayed with respect to control subjects. The opposite was the rule in patients with lower brainstem lesions who had delayed or absent TBR and no abnormal findings in the SBR. The SBR is mediated through circuits in the upper brainstem. Study of the SBR can be helpful in the neurophysiological assessment of patients with mesencephalic lesions. Muscle Nerve 43: 196–202, 2011
The ADRICOSM Pilot Project: a coastal and river basin prediction system for the Adriatic Sea

The ADRICOSM project was launched in October 2001, and ended in March 2005, with the main objective of demonstrating the feasibility of a near real time operational marine monitoring and forecasting system at the shelf and coastal scales, with connections to river basin runoff and coastal town sewer systems. The basic system consisted of an efficient network for the collection of marine data such as in situ temperature and salinity profiles and satellite sea surface temperature, a regional (AREG) and shelf scale modeling system, a data assimilation system and finally a coastal scale modeling system. Every week AREG releases 7 day marine forecasts at 5 km horizontal scales, which are used to nest other hydrodynamic models toward the coastal scale. Two shelf models (ASHELF-1 and ASHELF-2) at a 1.5 km horizontal scale were nested in AREG in order to simulate (and in the future to forecast) shelf scale oceanographic features. Another important aspect of ADRICOSM was the integration of the Cetina river (Croatia) and urban sewage monitoring/ modeling (Split, Croatia) systems with the shelf marine model. This integrated model system was used to simulate the dispersion of sewer discharges from the urban area in the coastal waters for water management performance studies. ADRICOSM is one of the first integrated land and marine waters operational oceanographic systems able to meet the urgent needs for reliable integrated coastal forecasts for the effective management of marine areas.
Initial report of off-pump coronary artery bypass surgery as sole therapy for moderate ischemic mitral regurgitation: operative and intermediate-term outcome.

BACKGROUND Patients undergoing on-pump coronary artery bypass surgery (CAB) with coexistent moderate ischemic mitral regurgitation (IMR) have a significant mortality rate compared to patients without MR. The mortality rate is elevated both perioperatively (0%-12% mortality), as well as over a 1- and 2-year postoperative period (15%-25%). It is thought that some patients are best served by off-pump CAB (OPCAB); however, outcomes have not been reported for such patients with coexistent moderate IMR. METHODS We reviewed the independent database of patients undergoing OPCAB between 1995 and 2002 to find 989 patients, 17 (1.7%) of whom had moderate or moderately severe MR. Patients were contacted and clinical and echocardiographic data were obtained. RESULTS The patient group consisted of 11 men and 6 women (age, 65 +/- 15 years). The study group had a PA pressure of 52 +/- 14, creatinine of 1.6 +/- 0.7, and left ventricular ejection fraction of 43 +/- 18. Nine patients (53%) had advanced New York Heart Association (class III-IV) heart failure. Mortality rates perioperatively and at 1, 2, and 3 years were 0%, 6.25% (1/16), 12.5% (2/16), and 38% (4/8), respectively. At the time of this report, no patient had returned for a reparative procedure. CONCLUSION In patients felt to be best served by OPCAB with ischemic MR, operative and intermediate mortality rates are remarkably similar to those previously reported for on-pump series. These data underscore the continued need to understand which patients undergoing CAB require mitral valve problems to be addressed at the time of surgery.