Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple mechanisms of picrotoxin block of GABA‐induced currents in rat hippocampal neurons.

1. We have examined the effect of picrotoxin on GABA‐induced currents in dissociated rat hippocampal neurons. In addition, we used the putative picrotoxin receptor antagonist, alpha‐isopropyl‐alpha‐methyl‐gamma‐butyrolactone (alpha IMGBL), and the picrotoxin agonist, beta‐ethyl‐beta‐methyl‐gamma‐butyrolactone (beta EMGBL) to explore the mechanisms of picrotoxin's interaction with the GABA‐Cl‐ receptor‐ionophore complex. 2. The picrotoxin block of GABA current was use dependent, suggesting that the site of picrotoxin block is exposed by the conformational change initiated by GABA binding to the receptor. 3. The alkyl‐substituted butyrolactone antagonist, alpha IMGBL, selectively blocked the use‐dependent mechanism of picrotoxin effect. After the apparent complete inhibition of the use‐dependent effect, there was a residual picrotoxin effect that was independent of the time or concentration of GABA application. This indicates that the picrotoxin block of the GABA current is mediated by two different mechanisms. alpha IMGBL influences just one of these mechanisms. 4. The picrotoxin receptor agonist, beta EMGBL, exclusively blocked the GABA current in a use‐dependent manner. Consistent with a use‐dependent mechanism, the rate of onset of block increased with GABA concentration. Surprisingly, the fraction of GABA current block decreased with increasing GABA concentration. 5. These results suggest that the relationship of picrotoxin and gamma‐butyrolactones with the GABA‐Cl‐ receptor‐ionophore is quite complex. They are consistent with at least two possible models of agonist‐antagonist interactions. Both cases require different antagonist affinities for the various kinetic states of the GABA‐Cl‐ receptor‐ionophore. However, there is no need to require that either picrotoxin or beta EMGBL acts as an open channel blocker.
The toxicology of chromium with respect to its chemical speciation: A review

The properties of trivalent and hexavalent chromium are reviewed with respect to acute and chronic oral toxicity, dermal toxicity, systemic toxicity, toxicokinetics, cytotoxicity, genotoxicity and carcinogenicity. The hexavalent chromium compounds appear to be 10–100 times more toxic than the trivalent chromium compounds when both are administered by the oral route. Dermal irritancy and allergy are more frequently caused by contact with soluble hexavalent chromium compounds. The cytotoxicity of soluble and insoluble hexavalent chromium compounds to fibroblasts is 100‐1000 times greater than that demonstrated by trivalent chromium compounds. In short‐term tests, the hexavalent chromium compounds demonstrated genotoxic effects four times more frequently than did the trivalent chromium compounds. Carcinogenicity appears to be associated with the inhalation of the less soluble/insoluble hexavalent chromium compounds. The toxicology of chromium does not reside with the elemental form. It varies greatly among a wide variety of very different chromium compounds. Oxidation state and solubility are particularly important factors in considering the toxicity of chromium with respect to its chemical speciation.
Phylogeography unplugged: comparative surveys in the genomic era

In March 2012, the authors met at the National Evolutionary Synthesis Center (NESCent) in Durham, North Carolina, USA, to discuss approaches and cooperative ventures in Indo-Pacific phylogeography. The group emerged with a series of findings: (1) Marine population structure is complex, but single locus mtDNA studies continue to provide powerful first assessment of phylogeographic patterns. (2) These patterns gain greater significance/power when resolved in a diversity of taxa. New analytical tools are emerging to address these analyses with multi-taxon approaches. (3) Genome-wide analyses are warranted if selection is indicated by surveys of standard markers. Such indicators can include discordance between genetic loci, or between genetic loci and morphology. Phylogeographic information provides a valuable context for studies of selection and adaptation. (4) Phylogeographic inferences are greatly enhanced by an understanding of the biology and ecology of study organisms. (5) Thorough, range-wide sampling of taxa is the foundation for robust phylogeographic inference. (6) Congruent geographic and taxonomic sampling by the Indo-Pacific community of scientists would facilitate better comparative analyses. The group concluded that at this stage of technology and software development, judicious rather than wholesale application of genomics appears to be the most robust course for marine phylogeographic studies. Therefore, our group intends to affirm the value of traditional (''unplugged'') approaches, such as those based on mtDNA sequencing and microsatellites, along with essential field studies, in an era with increasing emphasis on genomic approaches.
Innovation in non-Hodgkin lymphoma drug discovery: what needs to be done?

ABSTRACT Introduction: A new generation of anticancer agents called target drugs has been recently developed for the treatment of non-Hodgkin lymphomas. Current recovery rates in these diseases are up to 70% with immunotherapy based on the anti-CD20 monoclonal antibody combined with standard chemotherapeutics. However, there are still refractory or relapsed patients. Recently, several novel anti-lymphoma agents have been developed. Choosing the most effective personalized therapy still remains a crucial challenge in hematology. Areas covered: New drugs can specifically target malignant cells and inhibit cancer cell growth, proliferation and survival by specific interactions with one or more target proteins. Recent clinical studies have illustrated promising outcomes for novel drugs used as single agents and in combination with traditional therapeutics. In this article, the authors discuss novel targeted therapies with a promising outcome in NHL patients that are becoming integrated into treatment paradigms. Expert opinion: The development of new treatment options may help to avoid cytotoxic chemotherapy entirely in some clinical settings. Multicenter studies should be continued to investigate small agents and pathways inhibitors as this will enable us to enhance not only the duration of the treatment response but also the quality of the extended survival.
Weighted distortion for robust video coding

Conventional motion estimation used in rate-distortion (RD) optimized video coding is formulated for an error-free environment. Special considerations have to be made when transmitting video in lossy networks. In this paper we demonstrate a novel method of weighting the distortion used in RD optimized motion compensated prediction. By determining an appropriate weighting factor, motion vectors are biased towards macroblocks that have less influence on the motion propagation path. We therefore propose tracking the influence that each macroblock has along the motion propagation path to determine the weights. When combined with random Intra Updating considerable performance improvements are unveiled in comparison with state of the art robust video schemes.
Detection of Nonrandom X Chromosome Inactivation

This unit describes a PCR‐based assay for distinguishing between the two X chromosomes in female cells and assessing the percentage of cells having each parental X chromosome active. Methylation of CpG residues in gene promoters is a major mechanism of transcriptional silencing. In mammalian female cells, hypermethylation is the way in which one X chromosome is inactivated. The X‐inactivation assay described in the relies on methylation sensitivity. In this unit, the highly polymorphic and therefore typically heterozygous (CAG)n region of the 5 end of the coding region of the human androgen receptor gene (HUMARA), at Xq11.2, is used to distinguish and compare the methylation activity of the X chromosomes.
Radiotherapy-induced tumors of the spine, peripheral nerve, and spinal cord: Case report and literature review

Background: The development of a secondary malignancy in the field of radiation is a rare but well-recognized hazard of cancer treatment. The radiotherapy-induced (RT-I) tumors are even more aggressive and potentially lethal than the primary tumor. To goal of this article is to report a case of RT-I neural tumor located in the peripheral nerve and spinal cord and to perform a literature review of the subject. Case Reports: Thirty-year male with symptoms of hypoesthesia and dysesthesia of the L5 nerve root distribution and previous treatment of a testicular seminoma 20 years previously. The lumbar magnetic resonance imaging showed the growth of a nerve root tumor. Surgery was performed, and a fusiform tumor was resected with clear margins. The anatomopathological and immunohistochemical studies were compatible with a malignant peripheral nerve sheath tumor. A total of 30 cases were included in the review. The mean age of the patients at diagnosis of the induced tumor was 39.36 (±16.74) years. Most were male (63.3%). The main type of primary disease was neural tumors (30%). The most common type of histology was fibrosarcoma (20.0%). No difference was found in age, gender, and time of diagnosis between neural and nonneural tumors. The mean survival after the diagnosis of the secondary tumor was 10.7 months (±13.27), and neural tumors had a longer survival period (P = 0.031). Conclusion: The current gold standard therapy is complete resection with clear margins, since most tumors do not respond to chemotherapy and RT. The neural type of RT-I tumor presented a longer survival period.
Abdominal Injuries

Introduction Changing patterns of warfare coupled with improvements in protective body armor have combined synergistically to decrease truncal and abdominal trauma in contrast to previous conflicts. Despite the many advances in protective body armor, penetrating abdominal trauma remains an inevitable component of war surgery. Rapid recognition and treatment of intraabdominal injuries are necessary to ensure maximal survival with the minimum amount of morbidity.
Prise en charge de la douleur : Quel outil de mesure adopté pour une évaluation optimale.

L’Organisation Mondiale de la sante recommande que chaque pays fasse de la politique de lutte contre la douleur cancereuse une priorite des 1986. Le choix de l’outil d’evaluation de la douleur a appliquer pour une estimation precise et objective de celle-ci est un probleme auquel se heurtent les praticiens quotidiennement. La revue bibliographique menee sur les bases bibliographiques Pubmed, Scopus et Science Direct a permis de dresser un panel de questionnaires avec des specificites d’utilisation et applicables a differents contextes cliniques et socio-culturels. Deux categories de questionnaires ont ete analysees. La 1 ere categorie comprend des questionnaires verbaux. Elle renferme entre autres les Mc Gill Pain Questionnaire, Brief Pain Inventory, European Organization Research and Treatment of Cancer et leurs variantes. Les deux premiers sont applicables a differents contextes cliniques. Le dernier groupe est adapte au contexte specifique du cancer avec ses differents modules, cancer du sein, de la thyroide ou autre cancer. La 2 eme categorie comprend des questionnaires bases sur l’approche iconique. Elle renferme entre autres Pictorrino, ODEON, Questionnaire de Tack et ses collaborateurs. Developpe respectivement pour des pathologies specifiques comme les pathologies Oto-Rhino-laryngiques, Ophtalmiques et gastriques. Les elements critiques a considerer dans l’option pour un outil ou un autre sont, le contexte clinique d’utilisation ou la pathologie en cause et l’objectif ou la dimension ciblee par l’evaluation de la douleur ou l’inconfort.
Calculation and Analysis of Can Losses of Canned Induction Motor

The canned induction motors are widely used in pharmaceutical, chemical, and nuclear fields. It is necessary to calculate the losses, particularly the can losses, accurately. Combining steady-state ac magnetic 2-D finite-element solutions with the can harmonic loss formulas derived in this paper, the can losses under rated voltage in various operating conditions are obtained. Then, the calculation results under various voltages in no-load condition are compared with the experiment data, which provides the basis for the further performance analysis and motor design.
Cloning and Functional Characterization of a Novel Rat Organic Anion Transporter Mediating Basolateral Uptake of Methotrexate in the Kidney*

We have cloned a cDNA coding for a novel member of organic anion transporter, designated OAT-K1, expressed specifically in the kidney of rats. The rat OAT-K1 cDNA (2788 base pairs) had an open reading frame encoding for a 669-amino acid protein (calculated molecular mass of 74 kDa) which shows 72% identity with the cloned rat liver organic anion transporter, oatp. Northern hybridization and reverse transcription-coupled polymerase chain reaction revealed that the rat OAT-K1 messenger RNA transcript is expressed predominantly in the kidney. By use of stable LLC-PK1 cell monolayers transfected with the rat OAT-K1 cDNA, the transporter was suggested to mediate basolateral uptake of methotrexate, an anionic anticancer drug, but not taurocholate, p-aminohippurate, prostaglandin E2, and leukotriene C4. The methotrexate transport by rat OAT-K1 was unaffected by the presence of Na+ or Cl− gradient. The methotrexate accumulation by the OAT-K1-expressing cells showed saturability with the apparent Km value of 1.0 μM. Folate, sulfobromophthalein, and 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) inhibited the methotrexate accumulation markedly. These findings suggest that the rat OAT-K1 is localized in the basolateral membranes of renal tubules, where it mediates renal clearance of methotrexate from the blood.
Melatonin effect on bone metabolism in rats treated with methylprednisolone

Abstract: The present study was undertaken to examine the effect of melatonin (25 μg/mL of drinking water, about 500 μg/day) on a 10‐wk long treatment of male rats with methylprednisolone (5 mg/kg s.c., 5 days/wk). Bone densitometry and mechanical properties, calcemia, phosphatemia and serum bone alkaline phosphatase activity and C‐telopeptide fragments of collagen type I (CTX) were measured. Both melatonin and methylprednisolone decreased significantly body weight (BW) and the combination of both treatments resulted in the lowest BW values found. Consequently, all results were analyzed with BW as a covariate. Densitometrically, methylprednisolone augmented bone mineral content (BMC), bone area (BA) and bone mineral density (BMD) in the entire skeleton, BMC in cortical bone, and BMC and BMD in trabecular bone. Melatonin increased BMC and BA in whole skeleton and BMC and BMD in trabecular bone. For BMC and BA of whole skeleton, BMC of cortical bone, and BMC and BMD of trabecular bone, the combination of glucocorticoids and melatonin resulted in the highest values observed. Femoral weight of rats receiving methylprednisolone or melatonin increased significantly and both treatments summated to achieve the greatest effect. In femoral biomechanical testing, methylprednisolone augmented ultimate load and work to failure significantly. Rats receiving the combined treatment of methylprednisolone and melatonin showed the highest values of work to failure. The circulating levels of CTX, an index of bone resorption, decreased after methylprednisolone or melatonin, both treatments summating to achieve the lowest CTX values found. Serum calcium increased after methylprednisolone and serum phosphorus decreased after treatment with methylprednisolone or melatonin while serum bone alkaline phosphatase levels remained unchanged. The results are compatible with the view that low doses of methylprednisolone or melatonin decrease bone resorption and have a bone‐protecting effect.
Changes in morphology, cell number, cell size and cellular estrogen content of individual littermate pig conceptuses on days 9 to 13 of gestation.

Days 9 to 12 of gestation in the pig are marked by a pronounced asynchrony among littermate embryos. Previously published studies have suggested that the most advanced embryos within a litter by d 12 synthesize greater amounts of estrogen. Embryonic estrogen secretion has been shown to advance endometrial secretions, which may adversely affect less-developed littermates. To date, however, no comprehensive study of the developmental pattern and synthetic activities of individual littermate embryos during this period has been conducted. Litters were collected from Yorkshire gilts on d 9 (n = 11), 11 (n = 10), 12 (n = 5) and 13 (n = 8). Size (greatest diameter), DNA content (cell number), protein:DNA ratio and estrone (E1) and estradiol-17 beta (E2) content were determined for each embryo. Embryo sizes (mm greatest diameter) were (x +/- SEM) 1 +/- . 1, 5.6 +/- . 7, 41.2 +/- 11.7 and 405.7 +/- 16.7 on d 9, 11, 12 and 13, respectively. The daily variation in embryo size, expressed as CV was 82% on d 9, 145% on d 11, 206% on d 12 and 46% on d 13. DNA per embryo increased progressively from d 9 to 13, whereas the protein:DNA ratio declined. Content of E1 and E2 per embryonic cell was greatest on d 11 and d 12 before declining markedly on d 13. Cell number and embryo size were correlated positively in embryos 1 to 7 mm (P less than .01) and embryos greater than 100 mm (P less than .01) but not in embryos 8 to 100 mm. (ABSTRACT TRUNCATED AT 250 WORDS)
Reliable and Fast Mapping of Keypoints on Large-Size Remote Sensing Images by Use of Multiresolution and Global Information

This letter proposes a multiresolution technique to address the high computational cost in remote sensing image registration. The scale-invariant feature transform is applied to detect keypoints and descriptors, and then, global information combined with descriptors is utilized to establish keypoint mappings. Keypoints are first classified according to their octaves. Then, in the lowest resolution, the keypoints of the largest octave are mapped with descriptors and the global information, giving an initial affine transformation T0. In the next octave, the keypoints of the second largest octave are mapped by employing T0 to narrow the space of matching keypoints. By this means, the process of establishing keypoint correspondences is conducted from one resolution (octave) to the next as the obtained transformation gets finer until we get to the highest resolution. Due to the high computational expense of computing global information, the proposed technique is important for aligning large-size remote sensing imagery. Experimental results show that the proposed method can achieve a comparable registration accuracy but with a less computational cost than directly building keypoint mappings on images of large size.
Ralstonia solanacearum Dps Contributes to Oxidative Stress Tolerance and to Colonization of and Virulence on Tomato Plants

ABSTRACT Ralstonia solanacearum, an economically important soilborne plant pathogen, infects host roots to cause bacterial wilt disease. However, little is known about this pathogen's behavior in the rhizosphere and early in pathogenesis. In response to root exudates from tomato, R. solanacearum strain UW551 upregulated a gene resembling Dps, a nonspecific DNA binding protein from starved cells that is critical for stress survival in other bacteria. An R. solanacearum dps mutant had increased hydrogen peroxide sensitivity and mutation rate under starvation. Furthermore, dps expression was positively regulated by the oxidative stress response regulator OxyR. These functional results are consistent with a Dps annotation. The dps mutant caused slightly delayed bacterial wilt disease in tomato after a naturalistic soil soak inoculation. However, the dps mutant had a more pronounced reduction in virulence when bacteria were inoculated directly into host stems, suggesting that Dps helps R. solanacearum adapt to conditions inside plants. Passage through a tomato plant conferred transient increased hydrogen peroxide tolerance on both wild-type and dps mutant strains, demonstrating that R. solanacearum acquires Dps-independent oxidative stress tolerance during adaptation to the host environment. The dps mutant strain was also reduced in adhesion to tomato roots and tomato stem colonization. These results indicate that Dps is important when cells are starved or in stationary phase and that Dps contributes quantitatively to host plant colonization and bacterial wilt virulence. They further suggest that R. solanacearum must overcome oxidative stress during the bacterial wilt disease cycle.
Mapping QTLs regulating morpho-physiological traits and yield: case studies, shortcomings and perspectives in drought-stressed maize.

Comparative analysis of a number of studies in drought-stressed maize (Zea mays L.) reporting quantitative trait loci (QTLs) for abscisic acid concentration, root characteristics, other morpho-physiological traits (MPTs) and grain yield (GY) reveals their complex genetic basis and the influence of the genetic background and the environment on QTL effects. Chromosome regions (e.g. near umc11 on chromosome 1 and near csu133 on chromosome 2) with QTLs controlling a number of MPTs and GY across populations and conditions of different water supply have been identified. Examples are presented on the use of QTL information to elucidate the genetic and physiological bases of the association among MPTs and GY. The QTL approach allows us to develop hypotheses accounting for these associations which can be further tested by developing near isogenic lines (NILs) differing for the QTL alleles. NILs also allow for a more accurate assessment of the breeding value of MPTs and, in some cases, may allow for the map-based cloning of the gene(s) underlying the QTL. Although QTL analysis is still time-consuming and resource-demanding, its integration with genomics and post-genomics approaches (e.g. transcriptome, proteome and metabolome analyses) will play an increasingly important role for the identification and validation of candidate genes affecting MPTs and GY.
Seven‐ to 10‐year Outcome of Decompressive Surgery for Degenerative Lumbar Spinal Stenosis

Study Design. Retrospective review and prospective follow‐up of 88 patients who had decompressive laminectomy with or without fusion from 1983 to 1986. Objective. To determine the 7‐ to 10‐year outcome of surgery for degenerative lumbar spinal stenosis. Summary of Background Data. There is limited information on the impact of surgery for lumbar spinal stenosis on symptoms, walking ability, and satisfaction, as well as reoperation. Methods. Patients completed standardized questionnaires in 1993 that included items about reoperations, back pain, leg pain, walking capacity, and satisfaction with surgery. Associations between preoperative demographic and clinical variables and outcomes 7 to 10 years after surgery were evaluated in univariate and multivariate analyses. Results. Average preoperative age was 69 years and eight patients received fusion. Of 88 patients in the original cohort, 20 (23%) were deceased and 20 (23%) had undergone reoperation by 7‐ to 10‐year follow‐up. Fifty‐five patients answered questionnaires. Average duration of follow‐up was 8.1 years. Thirty‐three percent of the respondents had severe back pain at followup, 53% were unable to walk two blocks, and 75% were satisfied with the results of surgery. The severity of current spine‐related symptoms was a stronger correlate of physical functional status at the time of follow‐up than age or nonspinal comorbid conditions. Conclusions. Seven to 10 years after decompressive surgery for spinal stenosis, 23% of patients had undergone reoperation and 33% of respondents had severe back pain. Despite a high prevalence of nonspinal problems in this elderly cohort, spinal symptoms were the most important correlate of reduced functional status.