Miracle-dz/UniFAR-FTUs huggingface dataset:
Polymorphisms of Paraoxonase (PON1) and Their Significance in Clinical Toxicology of Organophosphates

Paraoxonase (PON1) is an HDL-associated enzyme capable of hydrolyzing multiple substrates, including several organophosphorous insecticides and nerve agents, oxidized lipids, and a number of drugs or pro-drugs. Several polymorphisms in the paraoxonase (PON1) gene have been described, which have been shown to affect either the catalytic efficiency of hydrolysis or the expression level of PON1. This review discusses the relevance of these polymorphisms for modulating sensitivity to organophosphorous compounds. Animal studies characterizing the PON1 polymorphisms have demonstrated the relevance of PON1 in modulating OP toxicity and have indicated the importance of an individual's PON1 status (i.e., genotype and phenotype taken together) rather than genotyping alone. Nevertheless, direct confirmation in humans of the relevance of PON1 status in conferring susceptibility to OP toxicity is still elusive. Recent studies examining the involvement of PON1 status in determining OP susceptibility of Gulf War veterans, sheep dippers, and individuals poisoned with chemical warfare agents represent a step in the right direction, but more studies are needed, with better documentation of both the level of exposure and the consequences of exposure.
Circulating Osteoprotegerin and Soluble RANK Ligand in Systemic Sclerosis

Objective Microvascular damage is an early pathogenetic event in systemic sclerosis (SSc). The receptor activator of nuclear factor-κB ligand (RANKL)/RANK/osteoprotegerin (OPG) system is involved in vascular biology. Our aim was to assess OPG and soluble RANKL (sRANKL) serum levels in patients with SSc and healthy controls. Methods Sixty patients with SSc (median age 58, range 31–72 yrs) and 60 healthy subjects matched for age, sex, and menopausal status were recruited. Serum OPG, sRANKL, soluble vascular cell adhesion molecule (sVCAM; marker of endothelial activation/injury), and bone turnover markers were measured. Bone mineral density in patients was assessed and cardiovascular/coronary risk was estimated. Results OPG was similar in the 2 groups, while sRANKL and sRANKL/OPG ratio was higher in patients (p = 0.01 for both). sVCAM was markedly higher in patients (p < 0.001). OPG levels correlated positively with age in both patients (Spearman R = 0.50, p < 0.001) and controls (R = 0.56, p < 0.001). In patients, OPG was lower in men and higher in those with active ulcers or calcinosis. sRANKL levels were higher in patients treated with platelet aggregation inhibitors, and correlated negatively with densitometric measures. 25-hydroxyvitamin D levels were significantly lower in patients (p < 0.001). In patients, OPG levels correlated positively with cardiovascular and coronary risk (R = 0.28, p = 0.05 and R = 0.34, p < 0.01, respectively) and were higher in patients with hypertension and left ventricular hypertrophy. sVCAMlevels correlated positively with cardiovascular and coronary risk (R = 0.27, p = 0.06, and R = 0.38, p < 0.01, respectively). Conclusion Higher sRANKL levels and sRANKL/OPG ratio in patients with SSc are likely to be a consequence of altered bone microenvironment. We show a dissociation between the well established marker of endothelial activation/injury, sVCAM, and the alleged marker of vascular damage, OPG, in patients with SSc. Further studies are needed to better ascertain the relationships of the RANKL/RANK/OPG system with the progression of macro- and microvascular damage.
The postcoital copper-T.

The knowledge that the human ovum normally resides in the oviduct for 3 days formed the basis for the suggestion that the IUD might be useful as a morning-after contraceptive. A copper-T IUD was inserted in 97 women referred from colleges and high schools in western New York from 1 to 5 days after unprotected coitus. Rape cases were also studied. Analysis of the menstrual cycle when unprotected coitus occurred showed that college students tended to request a postcoital copper-T at about midcycle. Pregnancies were absent within 3 months of insertion among the 97 patients examined and treated with IUDs. Of the first 44 who were followed for 6 months 77% were still wearing the CU-T after 6 months of use and 69% still used it after 1 year. 5 of the init ial 50 devices were removed within 3 months because protection was only needed for the 1 unprotected coitus. The insertion of a copper-T to prevent pregnancy after unprotected coitus avoids unpleasant gastrointestinal side effects associated with other postcoital methods such as estrogen.
Prognosis of gastric cancer patients with node-negative metastasis following curative resection: outcomes of the survival and recurrence.

BACKGROUND The purpose of the present study was to provide valuable prognostic information on lymph node-negative gastric cancer patients following curative resection. METHODS Data from 112 lymph node-negative gastric cancer patients who underwent curative resection were reviewed to identify the independent factors of overall survival and recurrence. RESULTS The five-year survival rate of lymph node-negative gastric cancer patients was 85.7%, and recurrence was identified in 25 patients after curative surgery. The five-year survival rate of lymph node-negative gastric cancer patients was higher than that of lymph node-positive gastric cancer patients (P<0.001). Recurrence in lymph node-negative gastric cancer patients was less than that of lymph node-positive gastric cancer patients (P=0.001). The median survival after recurrence of lymph node-negative gastric cancer patients was longer than that of lymph node-positive gastric cancer patients (P=0.021). Using multivariate analyses, the following results were determined for lymph node-negative gastric cancer patients: sex, operative type and the presence of serosal involvement were independent factors of overall survival; and lymphadenectomy, number of dissected nodes and the presence of serosal involvement were independent factors of recurrence. CONCLUSIONS The prognosis of lymph node-negative gastric cancer patients was better than that of lymph node-positive gastric cancer patients. Male sex, subtotal gastrectomy and nonserosal involvement should be considered to be the favourable predictors of postoperative long-term survival of lymph node-negative gastric cancer patients. Conversely, limited lymphadenectomy, few dissected nodes and serosal involvement should be considered to be risk factors of postoperative recurrence of lymph node-negative gastric cancer patients.
Human granzyme B mediates cartilage proteoglycan degradation and is expressed at the invasive front of the synovium in rheumatoid arthritis.

OBJECTIVE To investigate the cartilage-degrading capacity of granzyme B and the presence of granzyme B-positive cells at sites of erosion in the rheumatoid synovium. METHODS Granzyme B was added to [(3)H]proline/[(35)S]sulphate-labelled cartilage matrices and to cartilage explants. Proteoglycan degradation was assessed by the release of (35)S and glycosaminoglycans into the medium and collagen degradation was assessed by the release of (3)H and hydroxyproline and by measuring the fraction of denatured collagen. Granzyme B expression was studied at the invasive front of the synovium by immunohistochemistry. RESULTS Granzyme B induced loss of both newly synthesized, radiolabelled proteoglycans in cartilage matrices and resident proteoglycans of the cartilage explants. No effect on collagen degradation was found. Granzyme B-positive cells were present throughout the synovium and at the invasive front. CONCLUSION The presence of granzyme B-positive cells at the invasive front of the synovium together with its ability to degrade articular proteoglycans supports the view that granzyme B may contribute to joint destruction in rheumatoid arthritis.
Operationalizing the Definition of Forest Degradation for REDD+, with Application to Mexico

The difficulty of defining and quantifying forest degradation is a major constraint in the implementation of the international mitigation mechanism Reduced Emissions from Deforestation and Forest Degradation (REDD+). Our aim is to develop an operational framework for defining and quantifying forest degradation at a local level for early REDD+ projects and for national REDD+ programmes, through a ground level approach. We critically review and discuss national and international definitions of forest and of forest degradation, and then analyze the main difficulties in making these operational, evaluating the key elements and threshold values that are used, and contextualizing them using Mexico as a case study. We conclude that, given the lack of historical biomass data and the limited capability for monitoring degradation using remote sensing, forest degradation is best measured against a local benchmark that represents areas of low or no degradation that have comparable biophysical characteristics. Use of benchmarks of this type could offer a quick-start option for local assessment and construction of reference levels for forest degradation. These could be refined as more data become available and could eventually be integrated into national monitoring systems.
Two-photon polymerization of microneedles for transdermal drug delivery

Importance of the field: Microneedles are small-scale devices that are finding use for transdermal delivery of protein-based pharmacologic agents and nucleic acid-based pharmacologic agents; however, microneedles prepared using conventional microelectronics-based technologies have several shortcomings, which have limited translation of these devices into widespread clinical use. Areas covered in this review: Two-photon polymerization is a laser-based rapid prototyping technique that has been used recently for direct fabrication of hollow microneedles with a wide variety of geometries. In addition, an indirect rapid prototyping method that involves two-photon polymerization and polydimethyl siloxane micromolding has been used for fabrication of solid microneedles with exceptional mechanical properties. What the reader will gain: In this review, the use of two-photon polymerization for fabricating in-plane and out-of-plane hollow microneedle arrays is described. The use of two-photon polymerization-micromolding for fabrication of solid microneedles is also reviewed. In addition, fabrication of microneedles with antimicrobial properties is discussed; antimicrobial microneedles may reduce the risk of infection associated with the formation of channels through the stratum corneum. Take home message: It is anticipated that the use of two-photon polymerization as well as two-photon polymerization-micromolding for fabrication of microneedles and other microstructured drug delivery devices will increase over the coming years.
Structural basis for tandem L27 domain‐mediated polymerization

The establishment of epithelial cell polarity requires the assembly of multiprotein complexes and is crucial during epithelial morphogenesis. Three scaffolding proteins, Dlgl, MPP7, and Mals3, can be assembled to form a complex that functions in the establishment and maintenance of apicobasal polarity in epithelial tissues through their L27 domains. Here we report the crystal structure of a 4‐L27‐domain complex derived from the human tripartite complex Dlg1‐MPP7‐Mals3 in combination with paramagnetic relaxation enhancement measurements. The heterotri‐mer consists of 2 pairs of heterodimeric L27 domains. These 2 dimers are asymmetric due to the large difference between the N‐ and C‐terminal tandem L27 domain of MPP7. Structural analysis combined with biochemical experiments further reveals that the loop αA‐αB and helix αB of the C‐terminal L27 domain of MPP7 play a critical role in assembling the entire tripartite complex, suggesting a synergistic tandem L27‐mediated assembling event. —Yang, X. , Xie, X. , Chen, L. , Zhou, H. , Wang, Z. , Zhao, W. , Tian, R. , Zhang, R. , Tian, C. , Long, J., Shen, Y. Structural basis for tandem L27 domain‐mediated polymerization. FASEB J. 24, 4806–4815 (2010). www.fasebj. org
Dynamic compression plate (DCP) fixation of propagating medial condylar fractures of the third metacarpal/metatarsal bone in 30 racehorses: retrospective analysis (1990-2005).

REASONS FOR PERFORMING STUDY An in-depth review of dynamic compression plate (DCP) fixation of propagating medial condyle fractures of the third metacarpus or metatarsus has not been previously reported. OBJECTIVES To describe the technique, evaluate short-term outcome and long-term race performance of racehorses that underwent DCP fixation for repair of propagating or spiralling medial condylar fractures of the third metacarpal (McIII) or metatarsal (MtIII) bone. STUDY DESIGN Retrospective case series. METHODS The surgical case records of 30 horses with propagating fractures of the medial condyle of McIII or MtIII were reviewed. Medical information included: age, breed, sex, presentation, how injury occurred (racing or training), surgical treatment and post operative complications. Racing information included: starts, top 3 placing and career earnings. RESULTS Long propagating fractures of the medial condyle of Mc/tIII were identified in 23 Thoroughbred (TB) and 7 Standardbred (STB) racehorses. The fracture spiralled proximally in 22 of 30 cases (73%). Standardbreds had a higher propensity for hindlimb involvement (71%), whereas TBs tended to have more front limb involvement (61%). Twelve of 30 (40%) horses raced post surgery. Career earnings were significantly lower for TB horses with medial condylar fractures; $34,916 when compared with the national average of $60,841 (P≤0.03). Overall, horses having DCP fixation for medial condylar fractures had less starts post surgery (3.1 TBs and 5.8 STBs) compared with the national average (7 TBs and 17.3 STBs) and decreased lifetime starts 13.4 (TBs) compared with 17.3 nationally. CONCLUSIONS Propagating medial condyle fractures can be repaired with plate fixation to potentially lessen the risk of catastrophic fracture destabilisation and return to racing can be expected in 40% of horses. Further prospective studies are warranted comparing lag screw fixation with DCP fixation for repair of severe medial condylar fractures of the metacarpus/metatarsus.
TRAF6 Is Required for TRAF2-Dependent CD40 Signal Transduction in Nonhemopoietic Cells

ABSTRACT The emerging role of CD40, a tumor necrosis factor (TNF) receptor family member, in immune regulation, disease pathogenesis, and cancer therapy necessitates the analysis of CD40 signal transduction in a wide range of tissue types. In this study we present evidence that the CD40-interacting proteins TRAF2 and TRAF6 play an important physiological role in CD40 signaling in nonhemopoietic cells. Using mutational analysis of the CD40 cytoplasmic tail, we demonstrate that the specific binding of TRAF2 to CD40 is required for efficient signaling on the NF-κB, Jun N-terminal protein kinase (JNK), and p38 axis. In fibroblasts lacking TRAF2 or in carcinoma cells in which TRAF2 has been depleted by RNA interference, the CD40-mediated activation of NF-κB and JNK is significantly reduced, and the activation of p38 and Akt is severely impaired. Interestingly, whereas the TRAF6-interacting membrane-proximal domain of CD40 has a minor role in signal transduction, studies utilizing TRAF6 knockout fibroblasts and RNA interference in epithelial cells reveal that the CD40-induced activation of NF-κB, JNK, p38, and Akt requires the integrity of TRAF6. Furthermore, we provide evidence that TRAF6 regulates CD40 signal transduction not only through its direct binding to CD40 but also indirectly via its association with TRAF2. These observations provide novel insight into the mechanisms of CD40 signaling and the multiple roles played by TRAF6 in signal transduction.
Developmental arrest of fertilized eggs from the B6.YDOM sex-reversed female mouse.

When the Y chromosome of a Mus musculus domesticus mouse strain is placed onto the C57BL/6J (B6) inbred background, the XY progeny develop ovaries or ovotestes but never normal testes during fetal life. While some of the hermaphroditic males become fertile, none of the XY females produces litters. Here, we examined the fertility and development of oocytes derived from the XY female mouse. With or without preceding injection of gonadotropins, female mice were mated with normal B6 males, and their embryos were recovered at various developmental stages. In vitro fertilization was performed with the eggs recovered from the oviduct after treatment with gonadotropins. Development of embryos was examined by both light and electron microscopy. The results indicate that the oocytes released from the B6.YDOM ovary were efficiently fertilized and often initiated the first cell cleavage, but all embryos died during early preimplantation periods. Even when oocytes were fertilized in vitro, minimizing their exposure to the XY oviduct/uterus environment, most embryos died at the 1- or 2-cell stage. A few exceptional embryos reached the 4- or 8-cell stage, but abnormalities were evident in both nuclear and cytoplasmic structures of all embryos. After cleavage, neighbouring blastomeres were only loosely associated, and microvilli were abundant at the intercellular interfaces. We postulate that oocytes of the B6.YDOM female mouse become defective during XY ovarian differentiation, and, hence, fail to proceed through normal embryonic development.
Effect of temperature and composition on thermal properties of carbon steel

To simulate steel continuous process (such as induction heating of steel wire) accurately, the relevant thermal properties of carbon steel (within 0.06 to 1.22 wt. % of carbon) were determined as a function of temperature and carbon contents by multiple regression analysis method in this paper. These properties included the thermal conductivity, specific heat, and coefficient of linear thermal expansion, which are discussed within the temperature range from 0°C to 800°C. The effect of composition on thermal conductivity, specific heat, and coefficient of linear thermal expansion is investigated respectively. The results indicate that it is carbon content, instead of other compositions, has a significant influence on the thermal properties of carbon steel. In addition, the effects of carbon content of steels on the thermal properties of carbon steels with different temperature sensitivity in the range 0°C to 800°C have been presented.
Diagnostik und Behandlung des Gestationsdiabetes entsprechend den aktuellsten Leitlinien

Zusammenfassung Gestationsdiabetes (GDM) ist eine der häufigsten Schwangerschaftserkrankungen mit steigender Prävalenz – nicht zuletzt wegen der bedenklichen Zunahme von Adipositas unter jungen Frauen. GDM ist aber auch eine der Schwangerschaftskomplikationen, über die in den letzten Jahren am meisten diskutiert wurde – mit den größten Kontroversen insbesondere zur Frage der Diagnostik. Auch die Ansichten über die Intensität der Stoffwechselkontrolle, die Blutzuckerzielwerte und die Indikation zur Insulintherapie gingen weit auseinander, sehr zum Leidwesen der Behandler und der Schwangeren. Die letzten fünf Jahre erbrachten durch die Veröffentlichung bahnbrechender Studien einen großen Erkenntnisgewinn, der sich weltweit in neuen Empfehlungen zur Diagnostik und Therapie des GDM niederschlägt. So auch in Deutschland: eine interdisziplinäre Arbeitsgruppe der Diabetologen, Geburtmediziner und Neonatalogen hat in Anlehnung an diese internationalen Empfehlungen die seit 2001 gültigen Leitlinien überarbeitet. Der nachfolgende Artikel stellt die wichtigsten prakti schenAspekte für das diagnostische und therapeutische Vorgehen vor.
Why Are More Women Working in Britain?

In Britain, female labor force participation rose steadily from the Second World War to 1977. To explain this, we estimate a pooled time-series, cross-section supply function for single-year age groups of women. The life-cycle pattern is explained quite well by the presence of children. At a second stage we try to explain the rising level of the cohort intercepts estimated at the first stage. Real wage growth may be an explanatory factor, as cross-section evidence suggests it should be. Finally, we point to the 15% rise in the relative pay of women in the mid-1970s caused by the Equal Pay Act. This did not cause the expected decline in the relative demand for female employees.
Digital model for interconnect analysis

The current modeling techniques for DSM interconnects are analog based and involve complex and heavy computations. Also analog models suffer from numerical instability and truncation errors. To tackle these issues we resort to digital modeling where the transfer function is obtained through difference equations and not based on poles and zeros. The digital model of the interconnect is simulated and the results are compared with SPICE simulation. We have applied this digital model for analysing the H-tree clock distribution. The simulation results are obtained for the interconnect and H-tree clock distribution based on proposed digital model. The results were compared with the corresponding Spice output. These results show that analog modelling has far higher time complexity than the digital model. The accuracy analysis shows that the digital model has the maximum error of 2.5 percentage to Spice.
Localización óptima de estaciones de medición de humedad del suelo mediante clasificaciones del relieve a partir de modelos digitales del terreno

Landforms are directly related to environmental processes that are developed on them, such as hydrology. To study these processes many techniques are used, as installation of monitoring stations for soil moisture, which have a high cost associated with both instrumental and assembly. From Digital Terrain Models (DTM) spatial analyses have been conducted in order to obtain geomorphometric landform classifications. These classifications have allowed the delimitation of areas of different soil moisture content and hydrological processes, according to the type of geomormophetric units. This has facilitated the selection of sites for the installation of soil moisture monitoring stations. Results have been verified by fieldwork. This technique appears as an effective tool for obtaining the potential location of different soil moisture content areas reducing time and economical costs associated with fieldwork and allow defining in advance the optimal areas for soil moisture monitoring installation. Tecnologías de la Información Geográfica: la Información Geográfica al Servicio de los Ciudadanos. Secretariado de Publicaciones de la Universidad de Sevilla. Sevilla 2010 906
Online Displays of Parallel Programs: Problems and Solutions

The continuous display of information derived from on-line monitoring presents problems that are more diicult to resolve than those associated with oo-line displays. Handling these problems requires a systematic approach aaecting both the displays and the monitoring system itself. This paper discusses the problems inherent in on-line display and the approach to them taken by the Falcon monitoring system.