viverrini

viverrini http://www.selleckchem.com/products/SB-203580.html infection than Lao-theung. This behavioral trait is known to be a potential risk for acquiring O. viverrini and other fish-borne trematode infections [15], [57], particularly in an area where several food-borne trematodes co-exist, such as Lao PDR [16]�C[18], [22]. It is also important to note that intestinal parasites varied according to people’s socioeconomic status. Interestingly, S. mekongi was significantly more prevalent among better-off study participants who live along the lower Mekong islands. On the other hand, as expected, the highest prevalence of soil-transmitted helminths, particularly A. lumbricoides and T. trichiura, were observed among the poorest living in the highlands. The latter finding is in line with observations reported from southern P.R.

China [31] and other parts of the developing world [58]. People belonging to the poorest wealth quintiles are at higher risk of infection with soil-transmitted helminths. Finally, we found a low prevalence of intestinal protozoa in our study cohort. These findings support the previous observations, which have shown low prevalence of pathogenic intestinal protozoa in Southeast Asia [23], [41], [59]. We conclude that multiparasitism is the rule in different eco-epidemiological settings of Champasack province, and most likely elsewhere in Lao PDR. The extent of multiparasitism and the high infection prevalence and intensity with a host of intestinal parasites, most importantly S. mekongi and O. viverrini are a public health problem. Consequently, a chemotherapy-based morbidity control program should be re-implemented without delay.

To consolidate progress and ascertain long-term sustainability, other control measures such as health education, improving access to clean water and sanitation in an intersectoral fashion must be considered. Supporting Information Informed consent form (0.04 MB PDF) Click here for additional data f
Fascioliasis, a zoonotic disease caused by a liver fluke infection of the species Fasciola hepatica and F. gigantica, is of considerable veterinary and public health importance [1], [2]. Owing to global changes, infections with Fasciola spp. appear to be emerging or re-emerging in several parts of the world [1]. An estimated 91 million people are at risk of fascioliasis, whereas the estimated number of infections shows a large range from 2.4 to 17 million [3].

Severe clinical complications in the chronic phase of a Fasciola infection include cholangitis, cholecystitis, jaundice, and biliary colic [1], [4]. In Egypt, fascioliasis is an important clinical problem, particularly among school-aged children living in rural areas of the Nile Delta [5], [6]. Prevalence rates of Fasciola infections have been reduced in recent years, explained by control measures put forth by the Egyptian governorates, Anacetrapib including triclabendazole administration [6].

Furthermore, at the time of this data collection, all subjects we

Furthermore, at the time of this data collection, all subjects were apparently healthy and none were taking FTY720 buy medications known to alter food and energy metabolism. Subjects were instructed not to modify their food intake or eating patterns throughout the study. The days recorded consisted of two days of training followed by a day of rest. Blood lipid profile All subjects were reported to a commercial biomedical Laboratory (HBM Inc, Kuwait) after a 12 hour overnight fast. Blood samples were drawn from the antecubital vein. Serum total cholesterol and triglycerides were analyzed by enzymatic techniques in a Hitachi 911/904 (Roche Diagnostics, Basel, Switzerland) according to the manufacturer’s protocol.

The high density lipoprotein fraction of cholesterol (HDL-C) was measured after precipitation of the very low density lipoprotein (VLDLC) and low density lipoprotein (LDL-C) fractions with phosphotungstic acid. LDL-C was precipitated with Biomerieux reagent. Hemoglobin values were measured using an automatic multi-parameter blood cell counter (Sysmex? KX-21). Maximal Oxygen Consumption (VO2 max) VO2 max was assessed using a modified Bruce protocol. This protocol began after a 2-min warm-up. Treadmill speed, grade, or both were increased every 2 minutes until cardiopulmonary fatigue was reached and O2 max was obtained. Criteria for attainment of VO2 max included a < 2 ml/kg increase in oxygen consumption (O2) with an increased work rate, a respiratory exchange ratio (RER) greater than or equal to 1.1, and/or the subject's inability to maintain this work rate.

VO2 max is expressed in ml/kg/min. Statistical analysis All data were presented as mean, standard deviations (SD) and �� standard errors of the mean (SEM). Differences in mean values of the Kuwaiti fencers in body composition and blood lipids profile were analyzed using the average of the sum of the normal range and by applying a one sample t-test. In addition, the mean dietary intake of different foods and VO2 max values were compared using the one sample t-test. All the variables were compared with the international norm applying a t-test for independent samples. A probability value of �� 0.05 was considered significant. Data was analyzed using the Statistical Package of Social Sciences (SPSS) version 17 (Chicago, IL).

Results The results of the present study showed a statistically significant difference in dietary Batimastat consumption between the athletes daily average nutrient intake and the recommended dietary allowances (RDA) The blood lipids profile, body composition (BMI and %body fat), and VO2 max were within the normal range in comparison with international norms. A complete description of the fencing players physical characteristics (mean and standard deviation), including age, height, weight, body mass index, percent body fat, and maximum oxygen consumption are illustrated in Table Table11.

18 A specific ASIP haplotype (AH) based on two single nucleotide

18 A specific ASIP haplotype (AH) based on two single nucleotide polymorphisms has been associated with red and blond selleck chemical hair, tanning sensitivity, and increased risk of skin cancer.19,20 Downstream of MC1R, a tyrosinase (TYR) is involved in both eumelanin and pheomelanin synthesis, while a tyrosinase related protein (TYRP1) is involved in eumelanin synthesis exclusively.21 Polymorphic variants of TYR and TYRP1 associate with blue eye color, increased skin sensitivity to sun, and melanoma risk.20 With reference to skin type, hair and eye color, the aim of this study was to assess the impact of MC1R variation on SCC risk in RT patients. Also the relationship between the naturally occurring variants of ASIP, TYR, and TYP1 and susceptibility to SCC was explored.

This is the first comprehensive report dedicated to the correlation between genetic variation associated with phenotypic traits and susceptibility to SCC risk in RT patients. Materials & Methods Study subjects All participants invited (n = 555) were recruited through the Norwegian Renal Registry. They were all above the age of 18 with functional renal grafts at time of invitation. At least one invasive SCC was diagnosed in 185 (33.3%) of the invitees. Two SCC negative controls were matched by gender, year of birth (+/? 3 years), and duration of grafts (+/? 3 years) for each case according to the incidence density sampling method.22 Among those who eventually volunteered to participate (n = 217; 39.1%), SCC was diagnosed in 80 patients (36.9%).

All study participants provided informed consent, delivered EDTA-blood for DNA analyses, and responded to a questionnaire reporting skin phototype, hair and eye color, and the presence of skin lesions considered as warts or ��warty-like�� lesions (Table 1). In short, the typing of skin refers to skin phototype 1 (SPT1) as white, always burns and never tans; SPT2 as having some tanning response, otherwise as SPT1; SPT3 have white skin with a gradual and moderate tanning potential with minimal burns; whereas SPT4 has light brown skin with good tanning response and minimal burns.23 The representation of transplant recipients with and without SCC were evenly distributed throughout the different therapeutic eras administrating azathiopurine (Aza), prednisone (Pred), cyclosporine A (CsA), mycophenolate mofetil, and tacrolimus (1968�C1983; Aza+Pred; 1983�C1985: CsA+Pred; 1985�C1987: CsA+Pred, or Csa+Aza+Pred, randomized; 1987�C2000: Csa+Aza+Pred; 2000-onwards: gradually conversion from Aza to mycophenolat mofetil, and CsA to tacrolimus).

Initial immunosuppression is normally used during the grafts entire life. The study was approved by the Regional Ethical Committee and performed according to the Helsinki declaration. Table 1 Clinical variables and phenotypic characteristics of renal Dacomitinib transplant patients with (SCC positive) and without (SCC negative) squamous cell carcinoma of the skin.

CM were maintained at 37��C in an atmosphere of 5% CO2 and air an

CM were maintained at 37��C in an atmosphere of 5% CO2 and air and the medium replaced every 24 h. Then, untreated and treated infected CM were fixed and stained with Giemsa solution and the mean number of infected host cells and of parasites per infected cells scored as reported [12]. Only characteristic parasite nuclei Erlotinib cancer and kinetoplasts were counted as surviving parasites since irregular structures could mean parasites undergoing death. The drug activity was estimated by calculating the infection index (II – percentage of infected cells times the average number of intracellular amastigotes per infected host cell) [12]. All assays in vitro were run at least twice in duplicates. Mice acute toxicity NOAEL (No Observed Adverse Effect Level) was evaluated using male and female Swiss Webster mice (20�C23 g).

On day 1, one female and one male mice were treated with DB1965 under two therapeutic schemes: (i) injection via intraperitoneal (ip) every 2 h, with increasing doses, starting at 25 mg/kg up to 400 mg/kg and (ii) administration by ip or per oral (p.o) at doses ranging 25�C400 mg/kg [11]. Additionally, male mice (n=5 for each group) were treated with 20 daily consecutive doses with vehicle (only DMSO and water), 5 mg/kg DB1965 (ip), 50 mg/kg Bz (p.o) and with both combined compounds (5 mg/kg DB1965 ip+50 mg/kg Bz p.o). In all schemes, mice were inspected for toxic and sub-toxic symptoms according to OECD guidelines (Organization for Economic Co-operation and Development). Forty-eight hours after compound injection, the NOAEL values were determined [11].

Mice infection and treatment schemes Male Swiss mice were obtained from the Funda??o Oswaldo Cruz (FIOCRUZ) animal facilities (Rio de Janeiro, Brazil). Mice were housed at maximum 8 per cage and kept in a conventional room at 20�C24��C under a 12/12 h light/dark cycle. The animals were provided with sterilized water and chow ad libitum. Infection was performed by ip injection of 104 bloodstream trypomastigotes. The animals (18�C21 g) were divided into the following groups (at least five mice per group): uninfected (non-infected and non-treated); untreated (infected with T. cruzi but treated only with vehicle); and treated (infected and treated – ip and p.o – with 12.5 up to 100 mg/kg/day DB1965 or with 100 mg/kg/day benznidazole). For DB1965 treatment, mice received 0.1 mL ip injection or 0.

2 mL oral dose, starting at the 5 dpi followed by (i) for 5, (ii) 10 or (iii) 20 consecutive daily doses. For Bz treatment, infected mice received Cilengitide 0.2 mL oral dose (gavage) following the same therapeutic schemes as above described. Thirty days after compound administration, about 1000 ��L of blood were collected from the heart of anesthetized mice and then 500, 200 and 250 ��L were used for PCR, hemoculture and biochemical analysis, respectively [11].

The patients were excluded if they had: (1) concurrent hepatitis

The patients were excluded if they had: (1) concurrent hepatitis B or human immunodeficiency virus infections, autoimmune hepatitis, hemochromatosis, or Wilson��s disease; (2) systemic hypertension or if they reported current use of antihypertensive medication; (3) active alcohol consumption; former (4) antiviral or corticosteroid treatment; and (5) chronic renal disease or history of dialysis. The HCV patients who were candidates for treatment were given 180 ��g of peginterferon ��-2a (Pegasys?; Hoffmann-LaRoche, Basel, Switzerland) subcutaneously once weekly and ribavirin (Copegus?; Hoffmann-La Roche, Basel, Switzerland) at a daily oral dose of 1000 mg (body weight < 75 kg) or 1200 mg (body weight > 75 mg) for 48 wk. Laboratory measurement Testing for anti-HCV was carried out using a commercial ELISA kit (Axsym HCV version 3.

0; Abbott Laboratories, Chicago, IL, USA). All patients were HCV-G4 as detected by the Inno-LiPA HCV II assay (Innogenetics Inc., Alpharetta, GA, USA). Monitoring serum HCV RNA levels was by Amplicor (version 2.0, Hoffmann-La Roche) with a minimum detection limit of 50 IU/mL. Microalbuminuria was measured on a spot of second morning urine after an overnight fast, taking the mean of at least 2 samples collected for each subject. Urine albumin measurements were obtained by an automated immunoturbidometric assay (Roche Hitachi 902, Roche Diagnostics, Indianapolis, IN 46250 USA). For quantitative determination of creatinine in serum or urine, creatinine blanked kinetic Jaff�� (Roche Diagnostics, Hitachi 917, Modulator P analyzer Roche Diagnostics) was used.

We estimated GFR (eGFR) using the abbreviated modification of diet in renal disease equation. After an overnight fast, samples for cryoglobulin measurement were collected at a temperature of 37��C, centrifuged at 37��C for 10 min, and the serum separated; 5 mL of the serum was allowed to stand in a cryocrit tube at 4��C for 2-7 d, with formation of precipitate confirmed visually. If the test was positive we proceeded to electrophoresis and immunofixation for typing. All subjects were tested for cryoglobulin. Measures of renal insufficiency Three measures of renal insufficiency were examined, namely eGFR, microalbuminuria, and serum creatinine. Low eGFR was defined as eGFR < 60 mL/min every 1.73 m2.

The presence of microalbuminuria was tested using (1) albuminuria level; or categories of microalbuminuria, defined as individuals with an albuminuria level higher than the upper tertile of the albuminuria Carfilzomib level among controls (2) ACR: to adjust for the variation in urine concentration, microalbuminuria was assessed by ACR. Gender-specific values for the ACR were 2.2 mg/mmol for males and 2.8 mg/mmol for females. High levels of serum creatinine were defined as > 1.2 mg/dL for males and > 1.1 mg/dL for females. Outcomes and covariates definitions Subjects were considered diabetic if they had a fasting blood glucose level �� 5.

Unfortunately, the exact molecular mechanism of this ineffectiven

Unfortunately, the exact molecular mechanism of this ineffectiveness of IFN�� is still unknown. Currently, how to identify and use indicators to predict treatment response till has been widely concerned. In present study, we will evaluate the effectiveness of quantification of serum HBsAg in predicting the response of pegylated interferon ��-2a in HBeAg-positive CHB patients with prior lamivudine exposure, and the findings of this study would provide an important reference for helping CHB patients achieve sustained curative response. Patients and methods Patients HBeAg-positive chronic hepatitis B patients with prior lamivudine exposure and received pegylated interferon alfa-2a for recurring antiviral therapy were screened in this study, all of them were followed up at the Digestion Department of Chengdu Military General Hospital from January 2007 to December 2012.

The inclusion criteria were as follows: adults (18�C70 years), prior lamivudine exposure for more than 1 years, positive HBeAg statue, HBV DNA levels higher than 1.0��10^5 copies/mL, and elevated serum alanine amino-transferase (ALT) value. The exclusion criteria were as follows: ��co-infection with other hepatitis virus or human immunodeficiency virus; ��evidence of other causes of liver disease, such as autoimmune hepatitis and primary biliary cirrhosis; ��evidence of advanced liver diseases, such as decompensated cirrhosis, severe hepatitis, and hepatic carcinoma; ��poor compliance or no availability of detailed laboratory test results.

This study was carried out in accordance with the ethics committee of Chengdu Military General Hospital and informed consent was obtained from each participant. Study design and definition This is a prospective observational study, and all eligible participants were administered pegylated interferon alfa-2a (PegINF��-2a) (Roche Pharmaceuticals, Shanghai, China) at a dose of 180 ��g once a week by subcutaneous injection for 12 months. Quantification of serum HBsAg was carried out at baseline, months 3, 6 and at the end of treatment (12 months), and the quantitative HBV DNA and liver function was also assessed at each time-point. According to the follow-up outcomes in this study, patients were designated as either responders or nonresponders. Responders were defined as an ALT normalization, accompanying with HBeAg seroconversion at the end of treatment and the presence of a sustained virological response. Patients who did not achieve the above-mentioned criteria were defined as NRs. And sustained Batimastat virological response was defined as undetectable serum HBV DNA both at the end of therapy and 6-month of follow-up.

Thus in order to evaluate the HER-2 expression, the Remmele scale

Thus in order to evaluate the HER-2 expression, the Remmele scale (IRS) [15] modified by the authors and standardised Hercep test score modified for GC by Hofmann et al. were applied selleck chem inhibitor (Table 1) [16]. In IRS scale the intensity of color reaction and percentage of positive cells were taken into account. The score represented a product of points given for the evaluated characters and it ranged from 0 to 12 (Table 1). Cases with expression of 0 to 3 in IRS scale and with score 0 to 1+ according to Hofmann et al.’s criteria were treated as cases without overexpression (Table 2). It is well known that patients with gastric cancer have a heterogeneous HER-2 expression. Intratumoral heterogeneity of HER2 expression may potentially contribute to inaccurate assessment of HER2 status.

There is evidence that tumor heterogeneity is more common in gastric cancer (4.8%) than in breast cancer (1.4%) [16]. We observed 9% cases with heterogenous HER-2 immunoreactivity. Therefore, in some institutions the evaluation of HER-2 expression in the immunohistochemical staining is carried out using several sections of tissue sample. In our study single slide from large representative resection specimen for each cancer case was analyzed and 10% cutoff for the number of reactive cells was retained.Table 1Two procedures for evaluation of HER-2 expression.Table 2Parameters of HER-2 immunoreactivity.2.4. Statistical AnalysisStatistical analyses were performed using the Statistica 9.1 software (StatSoft Inc., Tulsa, OK, USA) and R language and environment for statistical computing (R Foundation for Statistical Computing, Vienna, Austria, http://www.

R-project.org/). Chi2 and Spearman rank correlation were used to analyze associations between immunohistochemical parameters of HER-2 Brefeldin_A expression and clinicopathological features. The overall survival rate was estimated by the Kaplan-Meier method. Multivariate analyses (Cox proportional hazard regression models) were also performed to assess the prognostic value of HER-2 expression and other clinicopathological features.3. Results3.1. HER-2 Expression in Gastric CancerThe HER-2 overexpression was detected in 23 (29.5%) tumors in Hercep test (IHC 2+/3+) and in 24 (30.7%) in IRS scale (IRS 4�C12) (Figure 1). Lack of HER-2 expression was found in 35 cases (44.9%). In all samples membrane localization of HER-2 in gastric cancer cells was dominantly observed, but cytoplasmic topography was also described (Table 2).Figure 1Immunohistochemical expression of HER-2 in gastric cancer tissue: (a) Hercept test: 1+, IRS: 4, ��200; (b) Hercep test: 2+, IRS: 8, ��200; (c) HercepTest: 3+, IRS: 12, ��200; (d) Hercep test: 3+, IRS: 12, ��200.3.2.

Figure 5Hospitalization age and lengths in higher (��10000 NT dol

Figure 5Hospitalization age and lengths in higher (��10000 NT dollar/day) and lower cost AMI patients from selleck products 1999 to 2008. Panel (a) shows the average age from higher and lower AMI hospitalization cost. Panel (b) shows the average hospitalization lengths …Figure 6The correlation of hospital length and total cost or daily cost in AMI patients. The hospital length was linearly correlated with total cost (a) and inversely correlated with daily cost (b).4. DiscussionIn this study, through the reliable nationwide population-based dataset, which almost covers entire population in Taiwan, we demonstrated that the hospitalization percentages of AMI and STEMI were declined from 1999 to 2008. In this period, the total admission number was increased, but the number of total AMI or STEMI admission was decreased.

Therefore, both factors contribute to the changes of AMI and STEMI admission percentage. The improvement would be caused by more aggressive risk factors control from medical systems and education on AMI prevention from the community and individual [1, 2]. However, this trend was more significant in male gender, which results in the near similar hospitalization percentages of AMI and STEMI between male and female in 2007~2008. This result may be caused by the gender differences because the hospitalization percentages of AMI and STEMI were lower in female than in male. Moreover, typical symptoms of coronary artery diseases or more attention and aggressive prevention in male gender may potentially result in the decline in MI or STEMI.

In contrast, NSTEMI was not significantly changed both in male and female, which indicated different pathophysiology between STEMI and NSTEMI. In this study, the patient age of MI with or without ST elevation was significantly increased over the 10-year period. Similar to those in the previous studies, the patient age was older in female than in male, Anacetrapib which implies the rather normal coronary artery and healthy life pattern in female than in male with the similar age. The decrease of AMI percentage of hospitalization and patient ages indicates that the improvement in treating coronary artery disease during this period. In contrast, the age of MI was reported to be similar within the 10-year period in USA [1].In this study, for the first time, we evaluated the hospitalization cost of AMI over the 10-year period. Surprisingly, similar hospitalization cost over the 10-year period for treating MI was observed. Since the budget for health insurance in Taiwan was increased and mild inflation was demonstrated in this period, the similar hospitalization cost for treating MI actually means that the medical fare for MI treatment was decreased in this period.

A malignant calibration set was similarly made by taking randomly

A malignant calibration set was similarly made by taking randomly 15 samples irrespective of whether they belong to stage II or stage III samples. PCA was carried out with each of these calibration www.selleckchem.com/products/PD-0332991.html sets. The PCA scores were used to simulate the profiles of each sample and the sum of squared residuals- ��p[Iop?Isp]2 calculated. Here Iop and Isp are the observed and simulated protein profile intensities, respectively, at point P on the time axis. All samples were now subjected to the Match/No match test using the three parameters, scores of factors, sum of squared residuals, and Mahalanobis distance [16]. The Mahalanobis distance is normally expressed in units of standard deviation.

It is given byD2=(Stest)M?1(Stest)��(1)where Stestis the vector of the scores and sum of squared residuals for a given test sample, and M given by M = ((S��S)/(n ? 1)), where Scontains the corresponding parameters for the calibration set of n standards. To test whether PCA and Discriminant Analysis can be used for objective discrimination between the different stages of malignancy we have also carried out the Match/No Match test with a standard set from Stage III samples alone. 12 samples were randomly selected from the 19 stage III group and PCA was carried out with 6 factors. Though sensitivity and specificity provide a good measure of the diagnostic accuracy, it is to be noted that use of these parameters lead to conflicting demands, since to improve one, the other may have to be sacrificed. Estimating diagnostic accuracy is very important in any kind of diagnostic test, since it gives an idea of how effectively a diagnostic test can differentiate disease from normal condition.

In order to arrive at the best values for sensitivity and specificity, one can apply the technique of Receiver Operating Characteristic (ROC) Curve [17]. We have carried out the estimation of the diagnostic accuracy for both normal and malignant set results by this method. One of the important measures of ROC analysis is finding Area Under the ROC-Curve (AUC), which evaluates the overall performance of the diagnostic test and is considered as the mean value of sensitivity for all the possible values of specificity [18]. The ROC curve analysis illustrates the relationship between the sensitivity and specificity of a diagnostic test. It is a measure of the performance of a diagnostic test. As already pointed out, the opposite trends of sensitivity and specificity make it difficult to arrive at suitable Batimastat threshold/cutoff values for the test parameters.

5 3 Improving Energy Consumption Structure The government should

5.3. Improving Energy Consumption Structure The government should make policies to promote industrial enterprises to reduce fossil energy consumption including coal and petroleum and improve the proportion of electricity consumption. It is also absolutely essential to vigorously www.selleckchem.com/products/BIBF1120.html develop clean energy such as nuclear, hydraulic, wind, and solar power.5.4. Establishing Energy and Environment Regulation Policies of Incentive CompatibilityThe regulation strategies based on sectors are better than those based on provinces in terms of regulation costs [11]. The emphases of regulation should be shifted to sectors in the short term and take market-oriented instruments of regulation (e.g., prices and taxes) in the long term and especially promote market-oriented reform of electricity and oil industry.

The government also should strengthen the pollution control on pollution-intensive industries, such as power production, nonmetallic manufacturing, ferrous metallurgy, paper manufacturing, food processing, and chemical industries which discharge lots of SO2 and COD.AcknowledgmentsThis study has been supported by the National Nature Science Foundation of China (Grant nos. 71002086, 71203224) and the Fundamental Research Funds for the Central Universities (Grant no. 12JNQM010).
Hyperchaos, characterized as a chaotic attractor with more than one positive Lyapunov exponent, was first reported by R?ssler [1]. Due to its great potential in theoretical and engineering applications, hyperchaos has been investigated extensively over the past three decades.

Since the hyperchaotic Brefeldin_A R?ssler system was reported, many more hyperchaotic systems have been proposed, such as hyperchaotic Chua’s system, hyperchaotic Chen system, and hyperchaotic LC oscillator system.Very recently, the authors [2] constructed a new 4D hyperchaotic system by adding one state variable into the 3D L�� chaotic system. The new hyperchaotic system is shown in the following form:x�B1=a(x2?x1)+x4,x�B2=cx2?x1x3,x�B3=?bx3+x1x2,x�B4=dx1+kx2x3,(1)where x1, x2, x3, and x4 are state variables; a, b, c, d, and k are system parameters, respectively. System (1) is dissipative and has only one equilibrium point (0,0, 0,0). When a = 35, b = 3, c = 12, d = 1, and k = 0.5, system (1) exhibits a hyperchaotic attractor, which is illustrated in Figure 1. Figure 1Hyperchaotic attractor for system (1).In recent years, chaos/hyperchaos synchronization has attracted increasingly attentions due to its potential applications in the fields of secure communication and optical, chemical, physical, and biological systems, and so forth [3�C5].