Lung cancer is the most common cancer

Lung cancer is the most common cancer in US and worldwide (Centers for Disease Control and Prevention and National Center for Health Statistics, 2013; American Cancer Society, 2014), and the survival rate is low (Howlader et al., 2013). Most cases (90%) of lung cancer are attributable to smoking (General, 2014). We demonstrate that quitting smoking is highly beneficial in reducing lung cancer risks for smokers regardless of their CHRNA5 rs16969968 genetic risk status. Evidence suggest that relative to individuals with CHRNA5 rs16969968 low-risk genotypes, those with high-risk genotypes are likely to smoke greater quantities, inhale more deeply, have more difficulty quitting, and have higher risk for lung cancer (Bierut et al., 2007; Saccone et al., 2010; TAG, 2010; Thorgeirsson et al., 2010; Thorgeirsson et al., 2008; Chen et al., 2012; Chen et al., 2015a; Hung et al., 2008a; Bloom et al., 2014). We now extend this evidence to show that quitting smoking produces essentially equivalent benefit regardless of cytochalasin d for this genetic risk factor. These results have potential value for preventive counseling with smokers; smokers with high-risk CHRNA5 genotypes can be informed that, on average, smokers with their genetic risk can largely eliminate their elevated genetic risk for lung cancer by quitting smoking. They can cut their risk of lung cancer in half and delay its onset by 7years, if they develop it. These results underscore the potential value of smoking cessation for all smokers, they elucidate the causal path from CHRNA5 risk to lung cancer diagnosis, and they have potential value for framing preventive interventions for those who smoke.

International Lung Cancer Consortium (ILCCO): The data management of ILCCO is supported by Cancer Care Ontario Research Chair awarded to R. Hung, and NIH U19 CA148127.
Transdisciplinary Research in Cancer of the Lung (TRICL). The TRICL study was supported by a grant from the National Institute of Health (U19CA148127). The Toronto study was also supported by Canadian Cancer Society Research Institute (no.020214), Ontario Institute of Cancer and Cancer Care Ontario Chair Award to RH. For the German Lung Cancer Study, funding for MD Anderson Cancer Study was provided by NIH grants (P50 CA70907, R01CA121197, R01 CA127219, U19CA148127, R01CA55769) and CPRIT grant (RP100443). The Harvard Lung Cancer Study was funded by the National Institutes of Health (CA074386, CA092824, CA090578. The National Key Basic Research Program Grant was funded by (2011CB503805) and the National Natural Science Foundation of China (30730080, 30972541, 30901233 and 30872178). MD Anderson was funded by NCI/NIH K07CA160753.
German Lung Cancer Study (Germany).
Germany Saarland ESTHER Study. This study was supported in part by the Baden-Württemberg State Ministry of Science, Research and Arts; by the German Federal Ministry of Education and Research.
Greater Toronto Area Lung Cancer study: This study was supported by Canadian Cancer Society Research Institute (no. 020,214) to R. Hung.
Hawaii Case-Control Study: This project was supported by Grant ROI-CA-55874 and Contract NOI-CN-05,223 from the United States National Cancer Institute and by Grant EDT-78 from the American Cancer Society.
Karmanos Cancer Institute, Wayne State University: The Karmanos Cancer Institute contribution was supported by the National Institutes of Health (NIH) (R01CA60691, R01CA87895, N01PC35145, P30CA022453).
Mayo Study, Mayo Clinic, College of Medicine: The contribution was supported by NIH-R01–80127/84354 and Mayo Foundation Fund.
NELCS: The New England Lung Cancer Study was funded by Grant Number P20RR018787 from the National Center for Research Resources (NCRR), a nondisjunction component of the National Institutes of Health (NIH).
Netherlands Radboudumc: The study was funded by an investment grant of Radboud university medical center.
Northern California Lung Cancer Study, University of California San Francisco (UCSF):

We first confirmed PDLIM overexpression in primary meningioma and

We first confirmed PDLIM2 overexpression in primary meningioma and schwannoma samples and showed that it is not expressed in HMC or normal meningeal tissue and minimally expressed in the Schwann cell examined. PDLIM2 was significantly knocked down in three primary meningioma and three primary schwannoma cell populations. This led to significant reductions in cell proliferation in both cell types. These results are in line with a previous study which showed how PDLIM2 suppression leads to decreased proliferation in androgen-independent prostate cancer cell lines (Kang et al., 2016). On the other hand, other studies have identified PDLIM2 as an important tumour suppressor (Sun et al., 2015; Zhao et al., 2016). Interestingly enough, PDLIM5, that we found highly overexpressed in the schwannoma phospho-proteome, was found overexpressed in gastric cancer cells and its siRNA-mediated silencing significantly reduced cellular proliferation (Li et al., 2015), highlighting a possible common role for this family as regulators of cell proliferation.
Our results showed that PDLIM2 can be phosphorylated. Recently one proteomic study identified specific phosphoserine sites on PDLIM2 (Bian et al., 2014); however, no phosphospecific pkc inhibitors are available and the result needs further validation.
Upon subcellular fractionation, PDLIM2 was found to localize into the nucleus, possibly exploiting E3 ubiquitin ligase activity (Tanaka et al., 2007). ICC analysis showed it localised to both the nucleus and the cytoplasm. It may be that PDLIM2 associates with the cytoskeleton and is thus rendered insoluble during subcellular fractionation, as is the case with some cytoskeletal proteins e.g. intermediate filaments, explaining why only nuclear PDLIM2 was detectable via Western blot. Our overall results indicate that PDLIM2 has both nuclear and cytoplasmic functions in meningioma cells. Additional studies will be performed to verify whether the protein acts on p65 even in Merlin-negative meningiomas and schwannomas, and the role of the phosphorylation on PDLIM2 activity.
The following are the Supplementary data related to this article.

Funding Sources


Gastric cancer (GC) is the fourth most common malignant cancer and the third most frequent cause of cancer-related deaths worldwide (Fock, 2014). Although the incidence of GC has decreased significantly in the past several decades, there remain approximately 723,000 GC-related deaths every year (Tan and Yeoh, 2015). This cancer is especially common in developing countries, particularly in Asia (Fock, 2014). At present, a combination of surgery, chemotherapy, and radiotherapy is used to treat patients with GC, yet a satisfactory therapeutic effect has not been achieved because it is a highly complex disease. This complexity makes it challenging to investigate the molecular mechanisms underlying gastric carcinogenesis and progression, which are multistep processes involving numerous genetic and environmental factors. Understanding the molecular regulation of GC development is crucial for GC diagnosis and treatment.
Methyl-CpG binding protein 2 (MeCP2), a member of methyl-CpG-binding domain (MBD) family, is a plentiful mammalian protein with two main domains: a MBD and a transcriptional repression domain (TRD) (Wakefield et al., 1999; Free et al., 2001; Adkins and Georgel, 2011; Vieira et al., 2015). As a key epigenetic regulator, MeCP2 regulates chromatin organization and gene transcription by binding to methylated DNA (Yasui et al., 2007; Hite et al., 2009), or gene promoters (Chahrour et al., 2008; Mellén et al., 2012). MeCP2 is a genetic cause of a variety of neurological disorders, such as Rett syndrome, and its role in neuronal systems has been well studied (Gadalla et al., 2011). It is reported to be a master regulator of gene expression. On the one hand, MeCP2 functions as a transcriptional repressor by binding methylated CpG dinucleotides and recruiting co-repressors, such as HDAC and Sin3A, to the promoter region to inhibit the expression of a variety of genes, such as BDNF and Cdkl5 (Ballas et al., 2005; Adams et al., 2007; Carouge et al., 2010). On the other hand, it acts as a transcriptional activator by binding methylated CpG islands and recruiting activators such as CREB1 (Chahrour et al., 2008; McGraw et al., 2011; Zachariah and Rastegar, 2012; Baker et al., 2013; Shin et al., 2013; Gabel et al., 2015).

br Data format The benchmark data are distributed in

Data format
The benchmark data are distributed in comma-separated value format (csv). Some basic description for each data set is also distributed in automated report files given in PDF format. The delimiter between fields in the csv files is the “,” symbol. The approximate size of the data set for a single scenario is 100Mb (50Mb in zip compression).
The data tables have the following columns:

This work was partially funded from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 216916: Biologically Inspired Computation for Chemical Sensing (NEUROChem), grant TEC2010-20886-C02- 02 and the Ramon y Cajal program from the Spanish Ministerio de Educación y Ciencia (RYC-2007-01475). CIBER-BBN is an initiative of the Spanish ISCIII.

Experimental design, materials and methods

To generate the dataset, we adopted a measurement procedure consisting of the following three steps. First, in order to stabilize the sensors and measure the baseline of the mao inhibitor response, we circulated synthetic dry air (10% R.H.) through the sensing chamber during 50s. Second, we randomly added one of the analytes of interest to the carrier gas and made it circulate through the sensor chamber during 100s. Finally, we re-circulated clean dry air for the subsequent 200s to acquire the sensors׳ recovery and have the system ready for a new measurement.
The sensor array was exposed to six different volatiles, each of them at different concentration levels (see Table 1). Table 2 shows the data distribution over the 36-month period. For processing purposes, the dataset is organized into ten batches, each containing the number of measurements per class and month indicated in Table 2. This reorganization of data was done to ensure having a sufficient number of experiments in each batch, as uniformly distributed as possible. Note that a few measurements, mainly in batch 7, appear at lower concentration levels than detailed in Table 2. This concentration mismatch is due to some experimental error. For the sake of completeness, we decided to include those samples in the dataset.

This work has been supported by the California Institute for Telecommunications and Information Technology (CALIT2) under Grant number 2014CSRO 136.

Value of the data

Data, experimental design, materials and methods


Value of the data

Experimental design, materials and methods

We compiled a very extensive dataset utilizing nine portable sensor array modules – each endowed with eight metal oxide gas sensors – positioned at six different line locations normal to the wind direction, creating thereby a total number of 54 measurement locations. In particular, our dataset consists of 10 chemical analyte species. Table 2 shows the entire list of chemical analyte as well as their nominal concentration values at the outlet of the gas source.
To construct the dataset, we adopted the following procedure. First, we positioned our chemo-sensory platform, ie the 9 sensing units, in one of the six fixed line positions indicated in the wind tunnel, and set the chemical sensors to one of the predefined surface operating temperatures. One of the predefined airflows was then individually induced into the wind tunnel by the exhaust fan, generating thereby the turbulent airflow within the test section of the wind tunnel. This stage constituted a preliminary phase that allowed to reach a quasi-stationary situation and to measure the baseline of the sensor responses for 20s before the chemical analyte was released. We then randomly selected one of the ten described chemical volatiles and released it into the tunnel at the source for three minutes. The chemical analyte circulated throughout the wind tunnel while recording the generated sensor time series. Note that the concentration reported in Table 2 represents only the concentration at the outlet of the gas source. Concentration disperses as the generated gas plume spreads out along the wind tunnel. After that step, the chemical analyte was removed and the test section was ventilated utilizing clean air circulating through the sampling setting at the same wind speed for another minute. Fig. 2 shows the typical response of the sensors after a complete measurement was recorded.

terbinafine hydrochloride The authors acknowledge the financial support of the Basic Science

The authors acknowledge the financial support of the Basic Science Research Program through the National Research Foundation (NRF) of Korea by the Ministry of Education (NRF-2015R1D1A1A01059165), Korea Research Fellowship Program through the NRF by the Ministry of Science, ICT and Future Planning (NRF-2015H1D3A1066311) and Incheon National University.


Experimental design, material and methods

The dataset contains 15 files of temporal series that represent 15 different situations related to 5 operational scenarios. Files’ duration varies depending on the situation and dysfunctional component. Accordingly, affected components are two types of depth sensor, the underlying network, or the whole subsystem. These situations can be wrongly understood by a decision maker, or only identified for instance after the malicious act was accomplished. Since wrongly managed situations might have significant adverse operational costs, it is critical to detect and analyze in real time such events. Datasets covering such situations are currently rare, because of the complexity to acquire data from cyber-physical systems. In our case, the principle of reusable experimental platform [1] was applied, to collect diverse datasets for monitoring [2] and categorization of aNomalies [3].

Experimental design, materials and methods
Two tanks of different volumes that function as storage and distribution device for water or fuel, one ultrasound depth sensor, four discrete sensors, and two pumps, were used to acquire the dataset (Fig. 1). A computer controlled the system with a PLC connected to a monitoring network. The ultrasound depth terbinafine hydrochloride on the main tank (volume of 7L) was calibrated relating the tank dimensions to 10,000 equidistant depth steps (0 corresponds to the full tank and 10,000 to the empty tank). Fig. 2 shows the tracked filling and emptying of the main tank. The four floating discrete sensors in the second tank (volume of 9L), measured levels of liquid corresponding to four volumes: 1.25L, 3.35L, 8L, and 9L.
All signals – ultrasound depth sensor, pump 1, pump 2, and the four discrete level sensors – were acquired synchroNously for every situation described in Table 1, independently of the affected component, operational scenario, and duration. The Normal scenario without aNomalies serves as reference. Nine situations focus on the ultrasound depth sensor, since its high resolution makes it more sensitive to show aNomalies (No. 2, No. 3, and No. 4). Also, objects intentionally hidden inside the main tank modify liquid volume measurements depending on the number of pieces (No. 5 and No. 6), while surrounding humidity can block the measure (No. 7). The ultrasound depth sensor measurements also change incorrectly when the tanks are hit with different intensities (No. 13, No. 14, and No. 15). Some terbinafine hydrochloride examples of signal alterations are represented in Figs. 3–5.
Additionally, two of the discrete sensors (1 and 2) were disrupted by keeping each one at a blocked position, i.e. up when the liquid has Not reached that level yet (No. 8) and pushing randomly down once liquid overflowed it (No. 9), leaving the tank almost empty or filling up to the security aperture, respectively. Network intrusions were carried out making use of the Modbus Penetration Testing Framework, Smod, to execute a denial of service attack (No. 10) and a spoofing attack (No. 11). Finally, aNomalies can also be the result of unintentional human errors as a wrong system connection (No. 12) and more generally incorrect maintenance. Technical data sheets of the ultrasound sensor and the PLC, the network schema, the transmitted information between components, a script written in Python to read and display files, and additional details are provided with the dataset.

The authors would like to thank the Chair of Naval Cyber Defense funded and supported by École Navale, Institut Mines-Telecom Atlantique Bretagne Pays de la Loire, Thales and DCNS.

There is also increasing evidence that the proliferation

There is also increasing evidence that the proliferation and dendricity of melanocytes is controlled by Mitf, which is regulated by MAPK signaling and stress-activated kinase p38 signaling. Therefore, it is possible that the signaling pathway of keratinocyte-derived factors through MK or p38 regulates Mitf in melanocytes and consequently controls the proliferation of mammalian epidermal melanocytes. Thus, melanocytes and keratinocytes form well-organized units in the RG7388 and hair follicles through cell-to-cell interaction.


Funding source

Recently, many topical depigmenting agents have been developed and widely applied for the amelioration of pigmentary dermatoses. Depigmenting formulations can be classified as either pharmacological agents or cosmetic agents. Hydroquinone (HQ) is a main component of topical pharmacological agents, which exhibits great efficacy, but has a relatively high rate of adverse side effect. For this reason, most of these formulations require a doctor\’s prescription. By contrast, cosmetic agents place more importance on safety, and therefore reduce adverse reactions by using nonirritant ingredients or using lower concentrations of irritant ingredients. Although these cosmetic agents can be used safely without a prescription, they are generally less effective than HQ-based pharmacological agents. The present article reviews current clinical usage of pharmacological and cosmetic depigmenting agents, as well as the current status of emerging depigmenting ingredients. In addition, we present laboratory data on the efficacy and safety of HQ and other cosmetic ingredients.

Pharmacological depigmenting agents

Cosmetic depigmenting agents

Comparative laboratory study of HQ and cosmetic ingredients

New approaches to developing depigmenting agents
The data described herein indicate that HQ is not a safe tyrosinase inhibitor and that it is necessary to develop novel topical agents for the treatment of pigmentary disorders. 4-n-Butylresorcinol may be used to produce a safe cosmetic agent, with the clinical efficacy required of a pharmacological agent. Furthermore, a multitarget approach is necessary because the combined use of two agents with different mechanisms of action can produce more powerful, additive effects. For example, 4-n-butylresorcinol acts mainly by inhibition of tyrosinase activity and has no effect on MITF. However, when combined with hinokitiol, an additive effect is produced which reduces MITF expression. The combination of two agents with different mechanisms may therefore be another useful strategy for increasing the efficacy of these agents.


This study was supported by a grant (HI10C0174, A100179) from the Good Health R&D Project, Ministry of Health and Welfare, Republic of Korea.

Skin color is an important social and cultural characteristic, which explains why the parents of children with any deviations from normal pigmentation are concerned about this problem. Troubles in skin color may raise considerable concern in black and Asian communities. Normal constitutive pigmentation is under the control of myriad genes, but recent studies in humans have attributed a major part of pigmentation variation across races to a limited number of genes. The human equivalent of the mutant golden zebrafish SLC24A5/NCKX5 explains a major part of the shift observed from Negroid to Caucasian phenotypes, and has recently been related to oculocutaneous albinism type 6. Other important human genes include MATP/SLC45A2, which when mutated is responsible for oculocutaneous albinism type 4, and the MRC-1 gene, several loss of function variants of which have been described to be associated with pale skin and red hair, indicating a skewing of melanin production toward that of pheomelanin. Although recreational sun exposure is contraindicated in babies, examination at birth may be misleading for congenital anomalies, because modifications of pigmentation are frequently revealed after the first outdoor exposures. Normal skin has essentially all its melanin in the epidermis and hairs. The color that one perceives when viewing the skin depends on several factors, especially the depth of pigment deposits. If melanin pigment is present in the dermis, the integument takes on a blue–gray hue that looks bluer as the pigment is deposited deeper. Melanin is not the only natural skin pigment. Diet carotenoids deposit in the epidermis and dermis, and contribute in a minimal way to the yellowish tint of the skin. However, a pronounced yellowing of the integument is common in babies on high carotenoid diets. Red and blue hues are the product of oxyhemoglobin and reduced hemoglobin in capillaries, arteries, and veins in the dermis. They may mix in some areas with abnormalities of the pigmentary system, such as in phakomatosis pigmentovascularis (Figure 1), and variations may depend on the maturation of the skin and its thickness.

hippo pathway The Hybrid cased charge split along

The Hybrid cased charge split along the axial grooves producing large heavy fragments (Fig. 15). The Buxton liner in the high mode generated regular shallow cuts into the case, but the cuts did not appear deep enough to promote regular fracture across the strips defined by the grooves. Occasionally the strips had fractured at a location of a Buxton liner formed cut, but the timing of the fracture was unknown.
When the Hybrid cased charge operated in the low mode, the case split in a similar manner. The Buxton liner again generated regular small cuts into the case (Fig. 16).

Case expansion
The Phantom camera images of the charges allowed the observation of the case expansion at early times. Measurements were taken to calculate the case radius at the grid position marked on the case of the charges, this gave up to four radius values at each position along the case length. At later times, obscuration prevented some measurements and limited how many times were measurable. The case radius from the trial has been compared with a GRIM 2D simulation for the high modes of both charge designs. Fig. 17 shows three times from the Hybrid high mode from round 7. The GRIM modelling results are plotted with a time offset from the experiment to take account of the detonator and pellet delay. This is assumed to be approximately 7 µs. The points from the experiment show some variation which is due to errors in measurement; however they show good agreement with the modelling. These data will also help validate the early expansion of the case for 3D modelling of the design. Low brisance explosives typically continue to accelerate fragments during the expansion of the explosive products; due to the early obscuration this assessment method would not be expected to yield a reliable measure of fragment velocity.

Velocity and blast results
In total the trial consisted of 9 firings; the first was a PE4 bare charge followed by the eight test charges. Table 5 shows a summary of the fragment velocities recorded by the velocity foils and the peak blast pressures recorded by the first two blast gauges.

The hippo pathway in peak pressures for the Hybrid design of ~33% was very similar to the value observed in the previous bare charge study [1] at ~35%. The similarity in the peak pressure reductions suggested that, when the case fracture is not delayed, both cased and uncased configurations operate in the same manner.


The authors would like to acknowledge the financial support of the Anglo-French Materials and Components for Missiles, Innovation and Technology Partnership (MCM ITP) program jointly funded by UK MoD (Dstl) and DGA.

The high strength of armour ceramics [1–3] makes it possible to partially or totally defeat high velocity projectiles directly at the surface of the ceramic material. This phenomenon is called interface defeat or dwell [4–17] and is an important defeat mechanism in, e.g., light armour applications.
One limitation when applying this in heavier armour designs is that it appears to be length scale dependent. Replica scaled impact experiments with unconfined ceramic targets show that the transition velocity, i.e., the velocity at which interface defeat ceased and ceramic penetration occurred, decreased as the length scale increased [11]. A probable explanation of the observed scale effect is that although maximum shear strength determines the upper bound for the transition from interface defeat to penetration, it is usually limited by the formation and growth of macroscopic cracks. Since the crack resistance of ceramic materials decreases with increasing length scale, in contrast to the otherwise scale-invariant stress field, the extension of a crack to a critical size will occur at a lower impact velocity in a larger target. An analytical model in [11] for the influence of length scale on the growth of a cone shaped modus I crack in thick unconfined ceramic targets gave reasonable results compared to the replica scaled impact experiments. The model showed that the projectile pressure at transition, i.e., the impact velocity at which the contact pressure exceeds the strength of the ceramic material and penetration initiates, is proportional to one over the square root of the length scale.

Por ejemplo las feministas objetan el hecho de que con

Por ejemplo, las feministas objetan el hecho de que con el tiempo los médicos hayan logrado medicalizar y controlar todos los aspectos de la vida reproductiva de las mujeres, desde la menstruación, la anticoncepción, el embarazo, el parto, la lactancia y la menopausia (véase Ehrenreich y English 1973; Todd 1989). Señalan que un efecto de este monopolio es boicotear los servicios de salud dirigidos AMG-900 cost mujeres, así como desacreditar y eliminar formas de cuidado alternativo que las mujeres han dado a otras mujeres en su papel de parteras y sanadoras homeopáticas. Otro efecto ha sido alterar las actitudes de las mujeres hacia sus propios cuerpos, con lo cual los han transformado en objetos que deben ser monitoreados y regulados con frecuencia, en lugar de que sea posible experimentarlos directamente como aspectos del ser. Las feministas también se oponen a los estereotipos de género que retratan a las mujeres como personas inmaduras, ignorantes, nerviosas y dependientes cuya conducta permea en la medicina e influye en las actitudes inconscientes de los médicos al momento de lidiar con pacientes del sexo femenino.
A pesar de que hay evidencia bien documentada de la existencia de patrones muy arraigados de comportamiento médico cuestionable, la mayoría de los especialistas en bioética eligen definir su papel a nivel local; es decir, evalúan o critican aspectos muy específicos de las prácticas de cuidado de la salud, pero evitan analizar los efectos sociales generales de la organización del cuidado de la salud en la sociedad. Luego presentan el examen que realizan de ciertas propiedades específicas del comportamiento médico en el marco de aceptación implícita de la organización básica de los servicios de salud, y eluden el tipo de evaluaciones del sistema de salud en su totalidad, mismo que sí presentan las feministas y otros críticos sociales.
Cuando abrimos la puerta de la bioética a investigaciones sobre cuestionamientos amplios y estructurales, como el feminismo nos alienta a hacerlo, comenzamos a examinar cuestiones tan importantes como la legitimidad de la organización jerárquica del sistema de salud. La estructura existente concentra el poder en las manos de una élite de hombres blancos privilegiados, al tiempo que depende del servicio obediente de un cuerpo amplio de personal de enfermería (en su mayoría mujeres blancas subordinadas), que a su vez tiene autoridad sobre el vasto personal de apoyo no profesional, en su mayoría perteneciente a minorías. Esta estructura y distribución de los roles no solo es inherentemente injusta, sino que forma parte de la contribución de la medicina a las estructuras sociales opresoras existentes. Por ejemplo, los problemas de salud que adquieren mayor importancia en los campos de la investigación y el tratamiento son en su mayoría riesgos de salud que amenazan a Transposition immunity los hombres blancos privilegiados (véase Rosser 1989). La investigación y los recursos médicos se encaminan al tratamiento y la reducción de riesgos relacionados con enfermedades como las cardiopatías, el cáncer y las apoplejías, pero no siempre se ponen al servicio del estudio de padecimientos que minan la fuerza y la energía de la población negra y nativa (véase White 1990; Beardsley 1990). Asimismo, buena parte de las iniciativas en el ámbito de las nuevas tecnologías reproductivas se ha encauzado hacia el desarrollo de medios que permitan que los hombres adinerados engendren hijos propios por medio de la implementación de tecnología riesgosa en mujeres; en contraste, cada vez son menos los recursos que se invierten en la identificación de estrategias para proteger la salud reproductiva de las mujeres y reducir la incidencia de la infertilidad en gente de todas las clases sociales (véase Stanworth 1987; Klein 1989).
Asimismo, en gran medida la discusión sobre bioética relativa a la distribución de los recursos de salud se ha llevado a cabo bajo el supuesto de que dichos recursos son un bien que debe maximizarse. Sin embargo, las feministas se alían con otros críticos sociales para cuestionar dicha premisa. El cuidado de la salud suele traer consigo efectos iatrogénicos; ciertamente, no siempre beneficia a sus destinatarios, además de que no siempre es cierto que más es mejor. Además, los pacientes que reciben cuidados suelen ser instados a confiar más de lo necesario en quienes les proveen los cuidados a su salud. Si la finalidad es mejorar la salud de la población y asegurar una distribución más justa de la buena salud, quizá concentrarse en la distribución de los cuidados a la salud no sea el medio más efectivo para lograrlo. La salud es producto de los cuidados a la salud y de la posición socioeconómica, pero también depende de la protección de ataques violentos y de toxinas en el medioambiente. La indigencia, las adicciones, la violencia y la falta de alimentación y vestimenta adecuadas son problemas cada vez mayores en Estados Unidos y traen consigo costos extraordinarios en términos de enfermedad y muerte. No obstante, aunque los servicios de salud costosos y de alta tecnología se están expandiendo para cubrir las necesidades de los privilegiados, los recursos para satisfacer las necesidades humanas básicas de los segmentos más desfavorecidos de la población van en descenso. Aun en Canadá, en donde el sistema de distribución de los recursos para el cuidado de la salud es mucho más equitativo que en Estados Unidos, las necesidades humanas básicas de alimentación, hospedaje y seguridad —todo lo cual es esencial para la salud— no siempre se satisfacen de manera adecuada.

br Method Subordinates from alpha banks

Subordinates from 5 alpha banks in Pakistan were taken as the population. The sample consisted of 224 subordinates from different branches and was selected on non-random purposeful sampling technique. As the questionnaire was in English language, only those employees were considered for this study who had the ability to understand and respond the questionnaire in English. Further, only those employees were considered for this study who were in the sample branch (under same manager) for at least six months. It is assumed that at least IOX2 cost six month duration is necessary to better understand one׳s leadership style. MLQ (Multifactor Leadership Questionnaire) 360 (5X short) by Bass and Avolio was used to collect data and was analyzed using SPSS 22.0. MLQ is a widely used questionnaire and MLQ 360 (5X short) is the latest version of this questionnaire. It is used to measure perceived transformational, transactional and laissez-faire leadership styles, satisfaction with leaders, leaders’ effectiveness and readiness to exert extra effort on job. This survey questionnaire is based on Bass׳s (1985) theory of transformational and transactional leadership. In this study, it is sued to examine the relationship between leadership styles (transformational, transactional, and laissez-faire) and outcome behaviors (satisfaction with leaders, their effectiveness, and readiness to exert extra effort). Descriptive statistics is used to demonstrate the demographics (gender, experience, age and education) of the study sample and inferential statistics (multiple regression technique) is used to test the hypotheses of this study. Additionally, zero-order correlation relationship between the leadership factors and outcome factors is also examined. The level of significance for multiple regression analysis to interpret the results is set at 0.05. The overall internal consistency (α) of the questionnaire was 0.85.

Demographic analysis reveals that banking sector of Pakistan is a male IOX2 cost sector. The majority of employees belonged to 26–35 years age group with Masters level education. The detailed summary of demographic results is presented in Table 1.

The findings of this study are context specific. The results reveal that banking sector of Pakistan is a male dominant sector with 67.29 percent of the respondents. However, this does not mean that banking sector of Pakistan offers limited growth opportunities for females, as a matter of fact number of females in the banking sector have increased recently according to previous research findings (Asrarulhaq, 2012; Bodla & Hussain, 2009). The majority of banking workforce (90.19%) belonged to 26–35 years age group. There was no subordinate with 46 or above age. It is revealed that due to early retirement and promotion of employees to management positions is the main reason for absence of higher age workforce in banking sector. In addition, increase in the number of banks in the country is also a significant reason. The same fact is reflected in education and experience factors as well. The education level of 88.73 percent subordinates was at least Masters, whereas only 11.27 percent of subordinates had bachelor degrees. The majority of respondents had one to eight years of experience at their current positions. Subordinates having one to four years of experience were 49.08 in percentage. The subordinates with five to eight years of experience at current designation characterized 28.70 percent of respondents. The inclusion of technology in banking sector, banks prefer to hire well educated and young workforce rather training the existing ones who are close to their retirement. In addition, some of the experienced managers were able to get promotion and were holding positions in administration, while many got retired with attractive retirement packages (offered by banks against their retirement before time) in last few years. Therefore, based on the above demographic results, it can be inferred that the banking sector of Pakistan is a growing sector and is boomed by the young generation.

Figure shows the increase in relative attenuation with

Figure 15 shows the increase in relative attenuation with increasing greenery ret proto oncogene at various distances from the source for buildings that were 4 and 12m high. The plots clearly show that building height has no significant effect on the resultant relative attenuation. This fact attributes the propagation characteristics to the lower parts of the building façade. The height of receiver points was set to be at the human ear level 1.8m from the ground. The results demonstrate a linear relationship between relative attenuation and the absorption coefficient of the vertical greenery system, with relative attenuation increasing with the absorption coefficient. This phenomenon is enhanced by increasing distance from the source location, which indicates that the effect of the installation of a vertical greenery system on street façades will be more efficient at remote locations. This phenomenon can be observed in actual urban environments where the resultant background noise originates from various remotely located sources.

A computer model based on the energy exchange theory was developed. Energy exchange was calculated using solid angle fraction measurements to account for the diffuse sound field present in the urban texture, given that all street façades are assumed to exhibit Lambertian diffuse reflections at higher orders of reflections. The urban texture was modeled as a simple rectangular building with lateral and longitudinal streets that intersect at right angles. Energy was distributed from a simple point source located somewhere in the urban setting for all visible façades. Furthermore, energy was exchanged through a network of nodes located at the center of each building façade, considering visibility and occlusion. Contour plots and results for an urban area with visual and geometrical characteristics similar to those of an Islamic pattern, such as a 410m×410m site with six lateral and six longitudinal streets with a building density of 73%, showed that the relative attenuation added after installing vertical greenery increased effectively near the source. However, the relative attenuation of remote locations from the source tended to have constant rates. The parametric investigation outlined the effect of applying vertical greenery to street façades. The effect of increasing building height was proven to add marginally to the relative attenuation rate, thus designating the propagation characteristics of sound to the lower parts of the street façades that are near the source and receiver levels. Further investigation also proved that the relative attenuation of vertical greenery is more effective at long distances from the source location, which is another benefit of installing vertical greenery on street façades in terms of dealing with remotely located sources in urban settings. Given that the simulations in this study are based on the outlined Islamic urban pattern characteristics, the attenuation rates related to installed greenery on street façades should not be cross-referenced to other urban pattern characteristics. In addition, less attenuation rates could be expected for urban patterns of wider streets because of the reduced surface area of relative façades in the urban scene and the wider street channel open to the sky. However, this assumption requires further investigation.

The primary purpose of buildings is to provide occupants with conducive, safe, comfortable, healthy and secured indoor environment to carry out different kinds of activities ranging from work, study, leisure and family life to social interactions. In order to achieve this purpose, buildings are designed, planned, constructed and managed based on standards and specifications established by governments, professionals and experts who are supposed to have adequate knowledge of users\’ needs and expectations. Studies (Kaitilla, 1993; Ukoha and Beamish, 1997; Zeiler and Boxem, 2008; Meir et al., 2009) have however shown that sometimes these standards and specifications do not conform to the changing needs and expectations of users; and thus users are not always satisfied with the performance of their buildings. The consequences of this are manifested in building related illness and ‘sick building syndrome\’ (Kian et al., 2001), increase in the desire for remodelling or modifications or abandonment of completed buildings (Kim et al., 2005) which may cause waste of energy and sometimes even damage to the building envelope components and the surrounding environment (Mitterer et al., 2012).

cathepsin inhibitors Discovery of longevity genes such as SirT gene

Discovery of longevity genes such as SirT gene family has resulted in tremendous enthusiasm among many scientists. Numerous studies have shown that this gene family uses intermediate metabolites such as acetyl-CoA, ATP, and NAD+ or nucleosomes to modify and control the activity and expression of cathepsin inhibitors involved in the central metabolic pathways. SirT gene can prolong lifespan by reducing catabolism. In contrast, the body can strengthen catabolism and cell proliferation during overnutrition so that it is inevitable to cause various diseases and even to shorten lifespan.
As emphasized by Ryan and Seeley [117], foods and nutrition are the basis for biological subsistence. Moreover, due to hormone-like activity, they transfer various signals to the body to control the metabolism and physiological activities through complicated interactions with the GI system and cell receptors in vivo. Meanwhile, many compounds from fruits and vegetables, although not considered as nutrients, regulate life activities such as appetite and basic metabolic status by interacting with receptors. Studies on these issues may provide us personalized nutrition and food recipes. Future research should focus on GPCRs, mTOR, TLRs, and nuclear receptors and their interactions with diet compositions. Studies on signal functions of all nutrients should also be performed.
After years of efforts, we have established a set of methods suitable for the functional evaluation of foods and drugs in vivo, i.e., intercellular wireless communication network. Because it is a directed weighted network, it enables us to quantitatively depict its characteristics by using various parameters from various angles by referring to biological macromolecular interaction network models, i.e., the undirected unweighted network and directed weighted metabolic network. Foods are closely correlated with nutritional metabolism. We have successfully created flux and flux control analysis suitable for the study based on the central metabolic pathway in human body. This established method can quantitatively evaluate the effects of foods on metabolic network because it quantitatively explores the roles of foods in synthesis and catabolism in vivo. In addition, because the analysis involves obtaining peripheral blood, it serves as a noninvasive method to provide a novel strategy for the quantitative evaluation of functional foods in vivo.

Medicinal use of citrus peels, such as aged tangerine peels in south east Asia, can be traced back to 10th century BC. However, the systematic in-depth exploration of the biological activity of citrus peels did not embark until the last decade, when advanced flavonoid profiles in citrus peels were established and isolation of majority of individual flavonoids became available. Since then, a plethora of biological properties important to health and diseases have been identified [1–3]. In addition to cancer prevention and intervention, other biological functions of compounds from citrus peels investigated include inflammation inhibition [4–7], hypolipidemia [8,9], regulation of metabolic syndrome [10–13], delayed onset of Alzheimer\’s disease [14,15] and more. Characterization of the phytochemical composition of citrus peels with modern analytical technology indicated that citrus peels are an abundant source of polyhydroxyl flavonoids (PHFs) such as hesperidin, neohesperidin and naringin; and almost the sole source of polymethoxyflavones (PMFs) with high content, which are mainly represented by nobiletin, tangeretin, sinesetin, 3,5,6,7,8,3′,4′-heptamethoxyflavone and 3,5,6,7,3′,4′-hexamethoxyflavone [3,16,17].
Research in anti-cancer activity of citrus flavonoids has been majorly focused on in vitro experiments to elucidate action mechanisms such as anti-proliferative effects, enzyme inhibition and cancer cell attenuation. PMFs have demonstrated the growth inhibition of human leukemic cell (HL-60) lines [18]. Of PMFs, tangeretin played important inhibitory roles in cancer-cell proliferation and metastasis stage by inhibiting cell adhesion and invasion [19]; showed cell cycle arrest in G1 phase by inhibiting cyclin-dependent kinases (Cdk) and enhancing Cdk inhibitor proteins [20]; inhibited extra cellular-signaling-regulated kinase 1/2 (ERK1/2) phosphorylation and growth of human mammary cancer cells and cytolysis by natural killer cells [21]; repressed induced and constitutively expressed cyclooxygenase-2 (COX-2) in human lung cancer cells [22]. In exploring the anticancer activity of citrus flavonoids, another major PMF, nobiletin was found to have effectively inhibited the proliferation and migration of human umbilical endothelial cells of human prostate, skin, breast and colon carcinoma cell lines [23]; reduced AOM-induced cell proliferation in colonic adenocarcinoma cells [24]; suppressed the proliferation, migration and tube formation on matrigel of human umbilical vein endothelial cells stimulated with endothelial cell growth supplement [25]; and attenuated the growth of prostate cancer cells and reduced azoxymethane (AOM)-induced large bowel carcinogenesis in rats [26], to name a few. Multiple biological pathways of anti-cancer mode of action by citrus flavonoids were also studied and summarized [27]. Furthermore, the study of structure activity relationship (SAR) of citrus flavonoids and cancer prevention was linked to the structural similarities between flavonoids and 17β-estradiol, suggesting interaction of flavonoids with estrogen receptors and also with estrogen metabolizing enzymes, such as cytochrome P450 enzymes CYP1A1 and CYP1B1, which are over-expressed in variety of tumor tissues [28].