The cooperative induction of hypoxia-inducible factor-1 alpha and STAT3 during hypoxia induced an impairment of tumor susceptibility to CTL-mediated cell lysis.

Hypoxia is an essential component of tumor microenvironment. In this study, we investigated the influence of hypoxia (1% PO(2)) on CTL-mediated tumor cell lysis. We demonstrate that exposure of target tumor cells to hypoxia has an inhibitory effect on the CTL clone (Heu171)-induced autologous target cell lysis. Such inhibition correlates with hypoxia-inducible factor-1alpha (HIF-1alpha) induction but is not associated with an alteration of CTL reactivity as revealed by granzyme B polarization or morphological change. Western blot analysis indicates that although hypoxia had no effect on p53 accumulation, it induced the phosphorylation of STAT3 in tumor cells by a mechanism at least in part involving vascular endothelial growth factor secretion. We additionally show that a simultaneous nuclear translocation of HIF-1alpha and phospho-STAT3 was observed. Interestingly, gene silencing of STAT3 by small interfering RNA resulted in HIF-1alpha inhibition and a significant restoration of target cell susceptibility to CTL-induced killing under hypoxic conditions by a mechanism involving at least in part down-regulation of AKT phosphorylation. Moreover, knockdown of HIF-1alpha resulted in the restoration of target cell lysis under hypoxic conditions. This was further supported by DNA microarray analysis where STAT3 inhibition resulted in a partly reversal of the hypoxia-induced gene expression profile. The present study demonstrates that the concomitant hypoxic induction of phospho-STAT3 and HIF-1alpha are functionally linked to the alteration of non-small cell lung carcinoma target susceptibility to CTL-mediated killing. Considering the eminent functions of STAT3 and HIF-1alpha in the tumor microenvironment, their targeting may represent novel strategies for immunotherapeutic intervention.

In vivo survival of teicoplanin-resistant Staphylococcus aureus and fitness cost of teicoplanin resistance.

Glycopeptide resistance, in a set of in vitro step-selected teicoplanin-resistant mutants derived from susceptible Staphylococcus aureus SA113, was associated with slower growth, thickening of the bacterial cell wall, increased N-acetylglucosamine incorporation, and decreased hemolysis. Differential transcriptome analysis showed that as resistance increased, some virulence-associated genes became downregulated. In a mouse tissue cage infection model, an inoculum of 10(4) CFU of strain SA113 rapidly produced a high-bacterial-load infection, which triggered MIP-2 release, leukocyte infiltration, and reduced leukocyte viability. In contrast, with the same inoculum of the isogenic glycopeptide-resistant derivative NM67, CFU initially decreased, resulting in the elimination of the mutant in three out of seven cages. In the four cages in which NM67 survived, it partially regained wild-type characteristics, including thinning of the cell wall, reduced N-acetylglucosamine uptake, and increased hemolysis; however, the survivors also became teicoplanin hypersusceptible. The elimination of the teicoplanin-resistant mutants and selection of teicoplanin-hypersusceptible survivors in the tissue cages indicated that glycopeptide resistance imposes a fitness burden on S. aureus and is selected against in vivo, with restoration of fitness incurring the price of resistance loss.

Guide to Cement-Based Integrated Pavement Solutions, August 2011

This guide provides a clear, concise, and cohesive presentation of cement-bound materials options for 10 specific engineering pavement applications: new concrete pavements, concrete overlays, previous concrete, precast pavements, roller-compacted concrete, cement-treated base, full-depth reclamation with cement, cement-modified soils, recycled concrete aggregates, and repair and restoration. Each application is presented as a method for meeting specific design and construction objectives that today’s pavement practitioners must accomplish. The benefits, considerations, brief description, and summary of materials, design, and construction requirements, as well as a list of sustainable attributes, are provided for every solution. This guide is intended to be short, simple, and easy to understand. It was designed so that the most up-to-date and relevant information is easily extractable. It is not intended to be used as a design guide for any of the applications identified herein. Recommendations for additional information that can provide such details are given at the end of each solution discussion. The intended audience is practitioners, including engineers and managers who face decisions regarding what materials to specify in the pavement systems they design or manage. The audience also includes city and county engineers, along with the A/E firms that often represent them, and state DOT engineers at all levels who are seeking alternatives in this era of changing markets.

Prescription footwear for severe injuries of foot and ankle: effect on regularity and symmetry of the gait assessed by trunk accelerometry.

After foot and/or ankle fracture, the restoration of optimal gait symmetry is one of the criteria of recovery. Orthotic insoles and orthopaedic shoes improve gait symmetry and regularity by controlling joint motion and improving alignment. The aim of the present study was to assess the effect of prescription footwear on gait quality by using accelerometers attached to the lower back. Sixteen adult patients with persistent disability after ankle and/or foot fractures performed two 30-s walking trials with and without prescription footwear (insoles and stabilizing shoes). Sixteen control subjects were also tested for comparison. The autocorrelation function was computed from the acceleration signal and the first two dominant periods were assessed (d1 and d2). Two parameters were used: (1) Stride Regularity (SR) which expresses the similarity between strides over time (d2), and (2) Stride Symmetry (SS) a ratio (d1/d2) which expresses the left/right similarity of gait independently of repeatability in the successive movements of each limb. In control subjects, SR and SS were 0.86+/-0.05 (correlation coefficient) and 81+/-10%, respectively. In the patient group, the effect of footwear was significant (SR: 0.88+/-0.06 vs. 0.90+/-0.05, SS: 38+/-23% vs. 46+/-27%). Pain was also significantly reduced (-34%). By using a rapid and low-cost method, we objectively quantified gait quality improvement after footwear intervention, concomitant to pain reduction. Substantial inter-patient variability in the footwear outcome was observed. In conclusion, we believe that trunk accelerometry can be a useful tool in the field of gait rehabilitation.

Effect of brushwood transposition on the leaf litter arthropod fauna in a cerrado area

The results of ecological restoration techniques can be monitored through biological indicators of soil quality such as the leaf litter arthropod fauna. This study aimed to determine the immediate effect of brushwood transposition transferred from an area of native vegetation to a disturbed area, on the leaf litter arthropod fauna in a degraded cerrado area. The arthropod fauna of four areas was compared: a degraded area with signal grass, two experimental brushwood transposition areas, with and without castor oil plants, and an area of native cerrado. In total, 7,660 individuals belonging to 23 taxa were sampled. Acari and Collembola were the most abundant taxa in all studied areas, followed by Coleoptera, Diptera, Hemiptera, Hymenoptera, and Symphyla. The brushwood transposition area without castor oil plants had the lowest abundance and dominance and the highest diversity of all areas, providing evidence of changes in the soil community. Conversely, the results showed that the presence of castor oil plants hampered early succession, negatively affecting ecological restoration in this area.

Coincident brane nucleation and the neutralization of Lambda

"static" instanton, representing pair creation of critical bubbles¿a process somewhat analogous to thermal activation in flat space. In that case, the branes may stick together due to thermal symmetry restoration, and the pair creation rate depends exponentially on the ambient de Sitter temperature, switching off sharply as the temperature approaches zero. Such a static instanton may be well suited for the ¿saltatory¿ relaxation scenario proposed by Feng et al.

2005 Annual Report Capitol Planning Commission, January 2005

The Capitol Planning Commission is authorized under Chapter 8A.371—378 of the Code of Iowa. “It shall be the duty of the commission to advise upon the location of statues, fountains and monuments and the placing of any additional buildings on the capitol grounds, the type of architecture and the type of construction of any new buildings to be erected on the state capitol grounds as now encompassed or as subsequently enlarged, and repairs and restoration thereof, and it shall be the duty of the officers, commissions, and councils charged by law with the duty of determining such questions to call upon the commission for such advice. “The commission shall, in cooperation with the director of the department of administrative services, develop and implement within the limits of its appropriation, a five-year modernization program for the capitol complex. “The commission shall annually report to the general assembly its recommendations relating to its duties under this section. The report shall be submitted to the chief clerk of the house and the secretary of the senate during the month of January.” —Code of Iowa, Chapter 8A.373

2006 Annual Report Capitol Planning Commission, April 2006

The Capitol Planning Commission is authorized under Chapter 8A.371—378 of the Code of Iowa. “It shall be the duty of the commission to advise upon the location of statues, fountains and monuments and the placing of any additional buildings on the capitol grounds, the type of architecture and the type of construction of any new buildings to be erected on the state capitol grounds as now encompassed or as subsequently enlarged, and repairs and restoration thereof, and it shall be the duty of the officers, commissions, and councils charged by law with the duty of determining such questions to call upon the commission for such advice. “The commission shall, in cooperation with the director of the department of administrative services, develop and implement within the limits of its appropriation, a five-year modernization program for the capitol complex. “The commission shall annually report to the general assembly its recommendations relating to its duties under this section. The report shall be submitted to the chief clerk of the house and the secretary of the senate during the month of January.” —Code of Iowa, Chapter 8A.373

2007 Annual Report Capitol Planning Commission, January 2008

The Capitol Planning Commission is authorized under Chapter 8A.371—378 of the Code of Iowa. “It shall be the duty of the commission to advise upon the location of statues, fountains and monuments and the placing of any additional buildings on the capitol grounds, the type of architecture and the type of construction of any new buildings to be erected on the state capitol grounds as now encompassed or as subsequently enlarged, and repairs and restoration thereof, and it shall be the duty of the officers, commissions, and councils charged by law with the duty of determining such questions to call upon the commission for such advice. “The commission shall, in cooperation with the director of the department of administrative services, develop and implement within the limits of its appropriation, a five-year modernization program for the capitol complex. “The commission shall annually report to the general assembly its recommendations relating to its duties under this section. The report shall be submitted to the chief clerk of the house and the secretary of the senate during the month of January.” —Code of Iowa, Chapter 8A.373

2010 Annual Report Capitol Planning Commission, January 2011

The Capitol Planning Commission is authorized under Chapter 8A.371—378 of the Code of Iowa. “It shall be the duty of the commission to advise upon the location of statues, fountains and monuments and the placing of any additional buildings on the capitol grounds, the type of architecture and the type of construction of any new buildings to be erected on the state capitol grounds as now encompassed or as subsequently enlarged, and repairs and restoration thereof, and it shall be the duty of the officers, commissions, and councils charged by law with the duty of determining such questions to call upon the commission for such advice. “The commission shall, in cooperation with the director of the department of administrative services, develop and implement within the limits of its appropriation, a five-year modernization program for the capitol complex. “The commission shall annually report to the general assembly its recommendations relating to its duties under this section. The report shall be submitted to the chief clerk of the house and the secretary of the senate during the month of January.” —Code of Iowa, Chapter 8A.373

Cricotracheal resection for adult and pediatric subglottic stenoses: Similarities and differences

Since the mid-1970s thoracic surgeons have used cricotracheal resection (CTR) in the adult population. Similar positive results have from then on been reported by different investigators using this technique. In contrast, otolaryngologists have typically used an anterior midline approach to the larynx and trachea for their laryngotracheal reconstructions (LTRs), both in adults and children. The fear of injury to the recurrent laryngeal nerve (RLN), the risk of a dehiscence of the anastomosis, and the interference with normal growth of the larynx in the pediatric age group were the main reasons put forward for not using a CTR for the cure of subglottic stenosis. In this article, we describe the similarities and differences in CTRs performed for adult and pediatric cases. The high rate (>90%) of success for severe pediatric SGS using CTR compares most favorably with LTR, which is still used in most otolaryngology departments. The reasons lie in the full resection of the stenosis and the restoration of a steady cartilaginous framework of the larynx and trachea with full mucosal lining on both sides of the anastomosis. Furthermore, CTR can be associated with a Rethi procedure for the cure of combined posterior glottic and subglottic stenoses. Good results from series of two different centers suggest that CTR will become the treatment of choice for pediatric severe SGS, as is presently the case in the adult population.

Traumatic recurrent anterior dislocation of the shoulder: two- to four-year follow-up of an anatomic open procedure.

The purpose of this study was to evaluate the results of an anatomic open stabilization procedure. Twenty-three consecutive patients with traumatic, recurrent, anterior glenohumeral instability were managed with a modified open procedure. All had a Bankart lesion. A standardized, true anatomic capsulolabral reconstruction was performed with suture anchors. Two patients were lost to follow-up, and twenty-one were evaluated after 36 months [range, 24-49 months] by an independent observer. Shoulder stability and function were the principal outcome measures. None of the patients had subsequent dislocations. All returned to full working capacity, and 19 reached their previous level of sport activities. The mean loss in active abduction and flexion was 1 degrees, in internal rotation, one vertebral level, and in external rotation, 7 degrees (arm at 90 degrees of abduction). Two patients had a positive anterior apprehension test. No sign of shoulder osteoarthritis was observed. The open anatomic capsulolabral reconstruction provides excellent results and allows the restoration of stability with good function.

Role of HIV-1-specific CD4 T cells.

PURPOSE OF REVIEW: Most of the studies investigating antiviral immunity have predominantly focused on CD8 T cells. However, numerous recent studies have highlighted the importance of HIV-1-specific CD4 T cells in the antiviral immune response, and have also revealed the high level of complexity and heterogeneity of the virus-specific CD4 T-cell responses. An understanding of the role of these key players in the antiviral immune response is of fundamental importance.RECENT FINDINGS: A comprehensive investigation of several features of virus-specific CD4 T-cell responses, including the magnitude, breadth, function and phenotype, has recently been performed. In particular, HIV-1-specific CD4 T-cell responses have been studied in different stages of HIV-1 infection, i.e. acute and chronic phase, under conditions of spontaneous (long-term non-progressors) or antiviral therapy-mediated control of virus replication or uncontrolled virus replication. Different phenotypical and functional patterns of HIV-1-specific CD4 T-cell responses were associated with different conditions of controlled versus uncontrolled virus replication, thus allowing the identification of signatures of protective immune responses. Robust and diverse virus-specific CD4 T-cell responses have been observed. These responses, however, were not predictive of nonprogressive versus progressive HIV-1-associated disease.SUMMARY: There is an urgent need to delineate the immune correlates of protective T-cell responses in order to develop novel immunological markers to evaluate the degree of immune restoration of antiviral therapy as well as the potential effectiveness of HIV vaccine-induced T-cell immune responses.

Una aproximació a l’estudi tècnic dels suports dels frontals d’altar romànics atribuïts als tallers de Vic i Ripoll

Aquest treball s’inclou dins la línia de recerca de la Secció de Conservació-Restauració delPatrimoni que es centra en l’estudi tècnic dels suports de fusta de frontals i retaules percaracteritzar-los i aportar noves informacions sobre els materials constitutius, els seussistemes de construcció i el seu origen. En aquest cas, l’estudi es centra en pintura sobretaula catalana del segle XII.La selecció de peces i l’acotació del tema van sorgir arrel d’un treball fi nal de màster (setembre2009) en el que ja es van estudiar els suports d’un conjunt de taules de fusta policromades dels segles XI, XIII i XIV custodiades al Museu Episcopal de Vic (MEV)...

La conservació del revers Criteris de restauració del suport de tela de la pintura catalana moderna com a testimoni històric i artístic

Cada quadre conté diferents tipus d’informació. El missatge estètic, materialitzat en la sevacapa pictòrica, és el que acostuma a ser objecte de valoració, crítica o simplement gaudi,però no és l’únic. Existeixen altres elements que poden donar-nos coneixement i que se situen al darrera d’aquest estrat pictòric. El suport de la pintura n’és un d’ells, i el revers, és la superfície d’aquesta matèria...