Miracle-dz/UniFAR-FTUs huggingface dataset:
RPA repair recognition of DNA containing pyrimidines bearing bulky adducts

Recognition of new DNA nucleotide excision repair (NER) substrate analogs, 48‐mer ddsDNA (damaged double‐stranded DNA), by human replication protein A (hRPA) has been analyzed using fluorescence spectroscopy and photoaffinity modification. The aim of the present work was to find quantitative characteristics of RPA–ddsDNA interaction and RPA subunits role in this process. The designed DNA structures bear bulky substituted pyrimidine nitrogen bases at the inner positions of duplex forming DNA chains. The photoreactive 4‐azido‐2,5‐difluoro‐3‐ pyridin‐6‐yl (FAP) and fluorescent antracenyl, pyrenyl (Antr, Pyr) groups were introduced via different linker fragments into exo‐4N of deoxycytidine or 5C of deoxyuridine. J‐dU‐containing DNA was used as a photoactive model of undamaged DNA strands. The reporter group was a fluorescein residue, introduced into the 5′‐phosphate end of one duplex‐forming DNA strand. RPA–dsDNA association constants and the molar RPA/dsDNA ratio have been calculated based on fluorescence anisotropy measurements under conditions of a 1:1 RPA/dsDNA molar ratio in complexes. The evident preference for RPA binding to ddsDNA over undamaged dsDNA distinctly depends on the adduct type and varies in the following way: undamaged dsDNA < Antr‐dC‐ddsDNA < mmdsDNA < FAPdU‐, Pyr‐dU‐ddsDNA < FAP‐dC‐ddsDNA (KD = 68 ± 1; 25 ± 6; 13 ± 1; 8 ± 2, and 3.5 ± 0.5 nM correspondingly) but weakly depends on the chain integrity. Interestingly the bulkier lesions not in all cases have a greater effect on RPA affinity to ddsDNA. The experiments on photoaffinity modification demonstrated only p70 of compactly arranged RPA directly interacting with dsDNA. The formation of RPA–ddsDNA covalent adducts was drastically reduced when both strands of DNA duplex contained virtually opposite located FAP‐dC and Antr‐dC. Thus RPA requires undamaged DNA strand presence for the effective interaction with dsDNA bearing bulky damages and demonstrates the early NER factors characteristic features underlying strand discrimination capacity and poor activity of the NER system toward double damaged DNA. Copyright © 2008 John Wiley & Sons, Ltd.
Coexistence of Neuropeptides and “Classical” Neurotransmitters

Coexistence is the phenomenon in which two or more neurotransmitters are present within the same neuron. The first demonstrations that neurons might have more than one transmitter came from studies of endocrine cells5 and of invertebrate ganglia. “ Immunocytochemical techniques have revealed at least thirty examples of coexistences in the mammalian central nervous ~ y s t e m . ~ The majority of investigations of coexistences have identified neuropeptides within the same neurons as “classical” neurotransmitters, e.g., cholecystokinin with dopamine in ventral tegmental neurons of the rat,* and galanin with acetylcholine in septohippocampal neurons of the rat. ’ Examples of two peptides coexisting with a “classical” neurotransmitter include substance P and thyrotropin releasing hormone with serotonin in medullary-spinal neurons of the rat,” and corticotropin releasing hormone and substance P with acetylcholine in dorsolateral tegmental neurons of the rat. ” Examples of two neuropeptides coexisting in neurons without demonstrated “classical” neurotransmitters have been identified, e.g., oxytocin and cholecystokinin in magnocellular hypothalamohypophyseal neurons of the rat,’* and neuropeptide Y and somatostatin in cerebral cortex neurons of the human.13 In addition, several examples of “classical” neurotransmitters coexisting within the same neuron have been identified, e.g., serotonin and gamma amino butyric acid (GABA) in the dorsal raphe nucleus of the rat,“ and acetylcholine (ACH) with GABA in the medial septum/diagonal band of the rat.I5 Some coexistences not normally seen have been revealed by disruption of normal afferent and efferent connections, or of altered hormonal environments, for example, the appearance of vasopressin in cholecystokinin-containing neurons of the paraventricular nucleus of the hypothalamus of the rat after adrenalectomy . Peptides may interact with “classical” transmitters at a variety of sites. Peptides could affect the synthesis, storage, release, or degradation of coexisting transmitters. Peptides could alter presynaptic reuptake sites, presynaptic receptors, postsynaptic receptors, or postsynaptic effectors. Many of these potential sites of interaction have been investigated, using both in vitro and in vivo methodologies. TABLE 1 gives selected examples of functional interactions which have been demonstrated between two or more transmitters localized within the same neuron.
Unique single-domain state in a polycrystalline ferroelectric ceramic

Non-180° ferroelectric domains are also ferroelastic domains; their existence in polycrystalline materials is to relieve internal stresses generated during solid-solid phase transitions and minimize the elastic distortion energy. Therefore, grains with random orientations in polycrystalline ceramics are always occupied by many domains, especially in the regions close to grain boundaries. In this Rapid Communication, we report the observation of a single-domain state in a BaTiO3-based polycrystalline ceramic at intermediate poling electric fields with in situ transmission electron microscopy. The grains in the virgin ceramic and under high poling fields are found multidomained. The unique single-domain state is believed to be responsible for the ultrahigh piezoelectric property observed in this lead-free composition and is suggested to be of orthorhombic symmetry for its exceptionally low elastic modulus.
Ionic basis for the electro‐responsiveness and oscillatory properties of guinea‐pig thalamic neurones in vitro.

The ionic requirements for electro‐responsiveness in thalamic neurones were studied using in vitro slice preparations of the guinea‐pig diencephalon. Analysis of the current‐voltage relationship in these neurones revealed delayed and anomalous rectification. Substitution of Na+ with choline in the bath or addition of tetrodotoxin (TTX) abolished the fast spikes and the plateau potentials, described in the accompanying paper. Ca2+ conductance blockage with Co2+, Cd2+ or Mn2+, or replacement of Ca2+ by Mg2+ abolished the low‐threshold spikes (l.t.s.). Substitution with Ba2+ did not significantly increase the duration of the l.t. s. , suggesting that under normal conditions the falling phase of this response is brought about by inactivation of the Ca2+ conductance. The after‐hyperpolarization (a.h.p.) following fast spikes was markedly reduced in amplitude and duration by bath application of Cd2+, Co2+ or Mn2+, indicating that a large component of this response is generated by a Ca2+‐dependent K+ conductance (gK[Ca]). Following hyperpolarizing current pulses, the membrane potential showed a delayed return to base line. This delay is produced by a transient K+ conductance as it can be modified by changing the drive force for K+. Presumptive intra‐dendritic recording demonstrated high‐threshold Ca2+ spikes (h.t.s.s.) which activate a gK[Ca]. Such h.t. s.s. were also seen at the somatic level when K+ conductance was blocked with 4‐aminopyridine. It is proposed that the intrinsic biophysical properties of thalamic neurones allow them to serve as relay systems and as single cell oscillators at two distinct frequencies, 9‐10 and 5‐6 Hz. These frequencies coincide with the alpha and theta rhythms of the e.e.g. and, in the latter case, with the frequency of Parkinson's tremor.
Is the aged rat ear more susceptible to noise or styrene damage than the young ear?

Noise- and styrene-induced hearing and hair cell loss were studied in young (3 months) and aged (24-26 months) Long-Evans rats. The animals were exposed 6 h/d, 5 d/w for 4 weeks to (a) broadband noise centered at 8 kHz (92 or 97dB SPL), or b) styrene (700 ppm). Auditory sensitivity was tested by recording evoked potentials from the inferior colliculus. Histological analyses of the organ of Corti, stria vascularis, and the spiral ganglions were also performed. Aged controls showed outer hair cell (OHC) loss at the basal and apical regions of the organ of Corti, and an increase in pigmentation concomitant to a decrease in vascularization of the stria vascularis, along with elevated thresholds relative to young controls. The 92-dB noise caused similar threshold shifts in both age groups, whereas the 97-dB noise caused more threshold shifts in the aged group compared to the young group. Recovery of the hearing thresholds depended both on the intensity of the noise and on the age of the animals. Aged rats had minimal hair cell loss as a result of styrene exposure, whereas young animals showed significant OHC loss, particularly in third row. Despite significant loss of OHCs, the young subjects showed styrene-induced threshold shifts only at high frequencies. In summary, the data show that : (a) there is an influence of age on both noise-induced and styrene-induced threshold shift and hair cell loss in rats and (b) the cochlea appear to have a redundancy in the number of OHCs, thus threshold shift does not necessarily occur with significant OHC loss.
Prolonged febrile seizures in the immature rat model enhance hippocampal excitability long term

Febrile seizures (FSs) constitute the most prevalent seizure type during childhood. Whether prolonged FSs alter limbic excitability, leading to spontaneous seizures (temporal lobe epilepsy) during adulthood, has been controversial. Recent data indicate that, in the immature rat model, prolonged FSs induce transient structural changes of some hippocampal pyramidal neurons and long‐term functional changes of hippocampal circuitry. However, whether these neuroanatomical and electrophysiological changes promote hippocampal excitability and lead to epilepsy has remained unknown. By using in vivo and in vitro approaches, we determined that prolonged hyperthermia‐induced seizures in immature rats caused long‐term enhanced susceptibility to limbic convulsants that lasted to adulthood. Thus, extensive hippocampal electroencephalographic and behavioral monitoring failed to demonstrate spontaneous seizures in adult rats that had experienced hyperthermic seizures during infancy. However, 100% of animals developed hippocampal seizures after systemic administration of a low dose of kainate, and most progressed to status epilepticus. Conversely, a minority of normothermic and hyperthermic controls had (brief) seizures, none developing status epilepticus. In vitro, spontaneous epileptiform discharges were not observed in hippocampal‐entorhinal cortex slices derived from either control or experimental groups. However, Schaeffer collateral stimulation induced prolonged, self‐sustaining, status epilepticus‐like discharges exclusively in slices from experimental rats. These data indicate that hyperthermic seizures in the immature rat model of FSs do not cause spontaneous limbic seizures during adulthood. However, they reduce thresholds to chemical convulsants in vivo and electrical stimulation in vitro, indicating persistent enhancement of limbic excitability that may facilitate the development of epilepsy. Ann Neurol 2000;47:336–344
Stochasticity in the miR-9/Hes1 oscillatory network can account for clonal heterogeneity in the timing of differentiation

Recent studies suggest that cells make stochastic choices with respect to differentiation or division. However, the molecular mechanism underlying such stochasticity is unknown. We previously proposed that the timing of vertebrate neuronal differentiation is regulated by molecular oscillations of a transcriptional repressor, HES1, tuned by a post-transcriptional repressor, miR-9. Here, we computationally model the effects of intrinsic noise on the Hes1/miR-9 oscillator as a consequence of low molecular numbers of interacting species, determined experimentally. We report that increased stochasticity spreads the timing of differentiation in a population, such that initially equivalent cells differentiate over a period of time. Surprisingly, inherent stochasticity also increases the robustness of the progenitor state and lessens the impact of unequal, random distribution of molecules at cell division on the temporal spread of differentiation at the population level. This advantageous use of biological noise contrasts with the view that noise needs to be counteracted. DOI: http://dx.doi. org/10.7554/eLife.16118. 001
INFORMAÇÕES técnicas sobre o arroz de terras altas: Estados de Mato Grosso e Rondônia safra 2007/2008.

Apresentacao. Importância economica. Clima. Solos. Preparo do solo e semeadura. Correcao e acidez e fertilizacao do solo. Cultivares. Irrigacao. Manejo de plantas daninhas. Doencas e metodos de controle. Pragas e metodos de controle. Colheita. Pos-colheita. Anexos.
The Ustilago maydis b mating type locus controls hyphal proliferation and expression of secreted virulence factors in planta

Sexual development in fungi is controlled by mating type loci that prevent self‐fertilization. In the phytopathogenic fungus Ustilago maydis, the b mating type locus encodes two homeodomain proteins, termed bE and bW. After cell fusion, a heterodimeric bE/bW complex is formed if the proteins are derived from different alleles. The bE/bW complex is required and sufficient to initiate pathogenic development and sexual reproduction; for the stages of pathogenic development succeeding plant penetration, however, its role was unclear. To analyse b function during in planta development, we generated a temperature‐sensitive bEts protein by exchange of a single amino acid. bEts strains are stalled in pathogenic development at restrictive temperature in planta, and hyphae develop enlarged, bulbous cells at their tips that contain multiple nuclei, indicating a severe defect in the control and synchronization of cell cycle and cytokinesis. DNA array analysis of bEts mutant strains in planta revealed a b‐dependent regulation of genes encoding secreted proteins that were shown to influence fungal virulence. Our data demonstrate that in U. maydis the b heterodimer is not only essential to establish the heterodikaryon after mating of two compatible sporidia and to initiate fungal pathogenicity, but also to sustain in planta proliferation and ensure sexual reproduction.
Evaluation of Herbal Neonatal Chick Care Against Iron-induced Toxicity in Broilers

A study was conducted to evaluate the protective effect of herbal Neonatal Chick care (NNCC) against iron-induced oxidative stress. A total of 130 day-old sexed male broiler chicks (Vencobb strain) were randomly divided into six groups consisting of 25 chicks each in groups 1-4 and 15 each in groups 5 and 6. Group 1 was maintained on basal diet, groups 2 and 3 on herbal NNCC at 6 and 8 g/chick/day, respectively, for 2 days immediately after hatching and later continued with basal diet up to 6 wk. Group 4 was given FeSO 4 at 0.5% of feed for 6 wk, while groups 5 and 6 were given NNCC as in groups 2 and 3, and later continued with the FeSO 4 as in group 4 for 6 wk. The concentration of thiobarbituric acid reactive substances (TBARS), protein carbonyls, glucose and calcium, and the activity of alanine transaminase (ALT) were significantly (P<0.05) increased in group 4 at the end of 6 th week, while the concentration of reduced glutathione (GSH), and the activities of superoxide dismutase (SOD) and catalase, phytohemagglutinin (PHA) index and HI titer were significantly (P<0.05) decreased in group 4. The NNCC treated groups (2, 3, 5 and 6) showed marked improvement in all the above parameters. It can be concluded that herbal NNCC offered protection and proved beneficial in resisting the adverse effects of stressor.
Breast Magnetic Resonance Imaging Incidental Findings

B reast magnetic resonance imaging (MRI) is now an integral part of breast imaging. It makes valuable contributions in high-risk screening; evaluating the extent of disease, positive surgical margins, and response to neoadjuvant chemotherapy; as well as distinguishing postoperative scar from recurrent disease. Although the examination is focused on the breast, portions of the neck, thorax, and upper abdomen are also visualized. Just as in computed tomography, the issue of the incidental or unexpected finding must be addressed by the reader. The detection of these findings during diagnosis and surveillance often results in additional testing, economic burden, and anxiety for the patient. Most incidentally detected lesions are benign; however, the reader must consider the potential of these findings to be metastases or additional primary tumors. Approximately 5% to 10% of breast cancers are metastatic at the time of diagnosis. Even with significant advances in breast cancer treatment, up to 70% of node-positive breast cancers will relapse and 20% to 30% of women with stage I and II disease will develop distant metastases, occurring approximately 15 years after radiation therapy. Therefore, all detected findings must be carefully considered. A recent study demonstrated the bone, lung, and liver to be the most common anatomical sites of distant metastases in patients with breast cancer, with 21.9% presenting with multisite involvement. The exception to this pattern is the basal-like and triple-negative breast cancers, which have a predilection for visceral and central nervous system metastases and infrequently involve bone. Although lesion detection occurs on potentially any sequence, the 3-dimensional fast spoiled gradient echo axial sequence is reported to be superior to the short tau inversion recovery sequence in incidental finding detection (82.8% vs 76.5%). As in computed tomography, the addition of intravenous contrast enhances lesion detection. Rinaldi et al demonstrated the enhanced 3-dimensional fast spoiled gradient echo axial fat-suppressed axial sequence to have greater sensitivity compared with unenhanced images in detecting metastatic lesions, especially those smaller than 10 mm (98.3% vs 79.3%). These lesions are often on the edge of the field of view and require window manipulation for identification.
An implementation of anonymous authentication system for Web services using proxies

This paper shows an implementation of the anonymous authentication system for Web services. This system uses privacy-enhancing digital signatures, called group signatures, which allow the user to be anonymously authenticated. Since the adopted group signature scheme utilizes novel cryptographic algorithms, the simple introduction of the authentication to the Web browsers and servers needs modifications of them. Thus, we use proxies in our implementation to avoid the modifications. We show that the authentication time is practical by the experiments.
APPLICATION OF A LOW COST AMPEROMETRIC SENSOR FOR DETECTION OF ALCOHOLS IN PROCESS RELATED HEADSPACE APPLICATIONS

A novel testing scheme to assure packaging integrity for liquid products was reoptimized using an amperometric sensor. The original method employed for this application uses a gas chromatograph with a surface acoustic wave sensor as the detector (GC/SAW) to monitor volatilized solvent vapors resulting from breaches in packaging integrity when subjected to moderate vacuum (20 in Hg). One common solvent in pharmaceutical products is ethanol. In the mode of “keeping it simple”, the new process design relies on the direct detection of ethanol using low-cost electrochemical gas sensor technology to replace the GC-SAW detector. The electrochemical sensor exhibits good selectivity to ethanol, thereby eliminating the need for a separation column, while the low detection limits allow for direct, near real time monitoring. The electrochemical sensor is an “environmentally green” technology requiring no high-purity mobile phase reagents, gases for the detectors or other consumable material. The instrument is both small and very low cost compared to GC based systems, and maintenance is simple. Analytical and operational specifications between the two methods are illustrated and compared to validate the electrochemical method for the package integrity application. The use of the electrochemical sensor in concert with vacuum chamber testing was fully characterized for leak testing. The parallel development investigations reported herein supported the goal of using the simple vacuum chamber system as a diagnostic tool to provide assurance of lot-scale product market container integrity without the need for individual inspection. Additionally, because of the success in using this sensor platform with leak testing, the scheme was further investigated for use with setting torque specifications for product vials as well as with a preliminary feasibility study to look at sensor’s utility with solvent drying operations. Introduction Regulated industries are becoming more proactive rather than reactive in gauging when manufacturing systems are operating outside their control range or specifications. Pharmaceutical manufacturing is leading this change. With the advances in process analytical technology, a process-based approach to quality is rapidly becoming the norm. (1-7) Recently, our laboratory developed and optimized a novel and efficient testing scheme to detect breaches in seal integrity for products dissolved or suspended in a volatile matrix. (8, 9) The test protocol was initiated as a feasibility investigation on how to empirically monitor the effectiveness of packaging seal operations. (8) The analysis method subjected each lot of containers of product solution to low vacuum, thereby drawing product from those containers unable to maintain seal integrity. This method was developed as a lot-scale method to supplement or replace current inspection protocols, whereby every product container fabricated and released
Markedly increased Oct4 and Nanog expression correlates with cisplatin resistance in oral squamous cell carcinoma.

BACKGROUND Oral squamous cell carcinoma (OSCC) is the sixth most prevalent cancer worldwide. Cancer stem cells (CSC) model theoretically contribute to tumor growth, metastasis, and chemo-radioresistance. Cisplatin is a widely used chemotherapeutic agent for OSCC treatment. The aim of this study was to compare stemness genes expression in chemo-sensitive and chemo-resistant specimens and further explore the potential markers that may lead to induce chemo-resistance in OSCC. METHODS The study method is the treatment of OC2 cells with cisplatin select cisplatin-resistant OC2 cells. Self-renewal ability was evaluated by cultivating parental and cisplatin-resistant OC2 cells within sphere-forming assay after serial passages. Differential expression profile of stemness markers between parental and cisplatin-resistant OC2 cells was elucidated. The parental and cisplatin-resistant OC2 cells were assessed for migration/invasion/clonogenicity tumorigenic properties in vitro. Expression of stemness markers in chemo-sensitive and chemo-resistant patients with OSCC was performed by immunohistochemistry staining in vivo. RESULTS Sphere-forming/self-renewal capability was increased in cisplatin-resistant OC2 cells. Cisplatin-resistant OC2 cells highly expressed the stemness markers (Nanog, Oct4, Bmi1, CD117, CD133, and ABCG2). Furthermore, cisplatin-resistant OC2 cells increased migration/invasion/clonogenicity ability. Notably, up-regulation of Oct4 and Nanog expression was significantly observed in cisplatin-resistant patients with OSCC (**P < 0.01). CONCLUSIONS These data indicate that cancer stem-like properties were expanded during the acquisition of cisplatin resistance in OSCC. Clinically, oral cancer stemness markers (Oct4 and Nanog) overexpression may promote the OSCC's recurrence to resist cisplatin.
Explicit diversification of image search

Search result diversification can increase user satisfaction in answering a particular information need. There are many ways of diversify search results. In some cases the user has a clear idea of how they would like to see their results diversified. This work presents a system that is capable of diversifying search results along specific user-specified axes of diversity.