A comparative in vitro study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells

Cancer frequently develops resistance to the majority of chemotherapy treatments.This study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors,specifically Canagliflozin(CAN),Dapagliflozin(DAP),Empagliflozin(EMP),and Doxorubicin(DOX),using in vitro experimentation.The precise combination of CAN+DOX has been found to greatly enhance the cytotoxic effects of doxorubicin(DOX)in MCF-7 cells.Interestingly,it was shown that cancer cells exhibit an increased demand for glucose and ATP in order to support their growth.Notably,when these medications were combined with DOX,there was a considerable inhibition of glucose consumption,as well as reductions in intracellular ATP and lactate levels.Moreover,this effect was found to be dependent on the dosages of the drugs.In addition to effectively inhibiting the cell cycle,the combination of CAN+DOX induces substantial modifications in both cell cycle and apoptotic gene expression.This work represents the initial report on the beneficial impact of SGLT2 inhibitor medications,namely CAN,DAP,and EMP,on the responsiveness to the anticancer properties of DOX.The underlying molecular mechanisms potentially involve the suppression of the function of SGLT2.

A review on therapeutic potential of Nigella sativa:A miracle herb

Nigella sativa(N.sativa)(Family Ranunculaceae)is a widely used medicinal plant throughout the world.It is very popular in various traditional systems of medicine like Unani and Tibb,Ayurveda and Siddha.Seeds and oil have a long history of folklore usage in various systems of medicines and food.The seeds of N.saliva have been widely used in the treatment of different diseases and ailments.In Islamic literature,it is considered as one of the greatest forms of healing medicine.It has been recommended for using on regular basis in Tibb-e-Nabwi(Prophetic Medicine).It has been widely used as antihypertensive,liver tonics,diuretics,digestive,anti-diarrheal,appetite stimulant,analgesics,anti-bacterial and in skin disorders.Extensive studies on N.sativa have been carried out by various researchers and a wide spectrum of its pharmacological actions have been explored which may include antidiabetic,anticancer,immunomodulator,analgesic,antimicrobial,anti-inflammatory,spasmolytic,bronchodilator,hepato-protective,renal protective,gaslro-prolective,antioxidant properties,etc.Due to its miraculous power of healing,N.sativa has got the place among the top ranked evidence based herbal medicines.This is also revealed that most of the therapeutic,properties of this plant are due to the presence of thymoquinone which is major bioactive component of the essential oil.The present review is an effort to provide a detailed survey of the literature on scientific researches of pharmacognostical characteristics,chemical composition and pharmacological activities of the seeds of this plant.

Nosocomial infections and their control strategies

Nosocomial infections are also known as hospital-acquired/associated infections. National Healthcare Safety Network along with Centers for Disease Control for surveillance has classified nosocomial infection sites into 13 types with 50 infection sites, which are specific on the basis of biological and clinical criteria. The agents that are usually involved in hospitalacquired infections include Streptococcus spp., Acinetobacter spp., enterococci, Pseudomonas aeruginosa, coagulase-negative staphylococci, Staphylococcus aureus, Bacillus cereus, Legionella and Enterobacteriaceae family members, namely, Proteus mirablis, Klebsiella pneumonia, Escherichia coli, Serratia marcescens. Nosocomial pathogens can be transmitted through person to person, environment or contaminated water and food, infected individuals, contaminated healthcare personnel's skin or contact via shared items and surfaces. Mainly, multi-drug-resistant nosocomial organisms include methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Pseudomonas aeruginosa and Klebsiella pneumonia, whereas Clostridium difficile shows natural resistance. Excessive and improper use of broadspectrum antibiotics, especially in healthcare settings, is elevating nosocomial infections, which not only becomes a big health care problem but also causes great economic and production loss in the community. Nosocomial infections can be controlled by measuring and comparing the infection rates within healthcare settings and sticking to the best healthcare practices. Centers for Disease Control and Prevention provides the methodology for surveillance of nosocomial infections along with investigation of major outbreaks. By means of this surveillance, hospitals can devise a strategy comprising of infection control practices.

Nigella sativa protects against isoproterenol-induced myocardial infarction by alleviating oxidative stress,biochemical alterations and histological damage

Objective: To evaluate the cardioprotective effect of Nigella sativa L.(N.sativa) in isoproterenol-induced myocardial infarction(MI).Methods: Groups were treated with different doses of ethanol extract of N.sativa(EENS)and N.sativa oil alone and along with enalapril for 28 days.MI was induced by subcutaneous administration of isoproterenol(85 mg/kg) in two consecutive doses.Levels of cardiac biomarkers and antioxidant enzymes such as creatine kinase–N-acetyl-L-cysteine, lactate dehydrogenase, aspartate aminotransferase, malondialdehyde, superoxide dismutase, reduced glutathione and catalase were evaluated along with gross histopathological examination.Results: Isoproterenol(85 mg/kg) induced MI by causing the significant(P < 0.01)reduction in the activity of cardiac biomarkers(creatine kinase–N-acetyl-L-cysteine,lactate dehydrogenase, aspartate aminotransferase) and antioxidant markers(superoxide dismutase, catalase, glutathione) along with significant(P < 0.01) increase in the level of malondialdehyde.Furthermore, histopathological evaluation also confirmed the isoproterenol-induced MI.Pretreatment with EENS(800 mg/kg) and combination of EENS(800 mg/kg) with enalapril(1 mg/kg) significantly(P < 0.01) prevented the development of these alteration and restored activity of cardiac biomarkers as well as antioxidant markers almost near to normal levels.Histopathological evaluation of cardiac tissue further confirmed the restoration of biochemical activity.Conclusions: Experimental findings thus indicate that EENS(800 mg/kg) demonstrated cardioprotective effect against isoproterenol-induced MI by restoring cardiac biomarkers and antioxidant status.

Quantification of total phenol,flavonoid content and pharmacognostical evaluation including HPTLC fingerprinting for the standardization of Piper nigrum Linn fruits

Objective:To carry out the physicochemical and phytochemical standardization with high performance thin layer chromatography fingerprinting of Piper nigrum L.(P.nigrum)fruits in order to ascertain the standard pharmacognostical parameters of this king of spices.Methods:Many standardization parameters like extractive values,total ash value,water soluble ash value and acid insoluble ash,moisture content,loss on drying and pH values of P.nigrum L.fruits were analyzed.The method of Harborne was adopted for the preliminary phytochemicals screening.Analysis of total phenolic and flavonoid contents,pesticides residues,aflatoxin and heavy metals were also performed.CAMAG-high performance thin layer chromatography system was used for fingerprinting of methanolic extract of P.nigrum L.fruits.Results:The results of phytochemicals testing indicated the presence of carbohydrates,phenolic compounds,flavonoids,alkaloids,proteins,saponins,lipids,sterols and tannins in various solvent extracts.Total phenolic and flavonoid contents in methanolic extract were found to be 1.728 1 mg/g and 1.087 ug/g,respectively.Heavy metals concentrations were found to be within standard limits.Aflatoxins and pesticides residues were absent.Conclusions:The outcome of this study might prove beneficial in herbal industries for identification,purification and standardization of P.nigrum L.fruits.

Cardiorenal syndromes

Cardiorenal syndromes (CRS) have been subclassified as five defined entities which represent clinical circumstances in which both the heart and the kidney are involved in a bidirectional injury and dysfunction via a final common pathway of cell-to-cell death and accelerated apoptosis mediated by oxidative stress. Types 1 and 2 involve acute and chronic cardiovascular disease (CVD) scenarios leading to acute kidney injury or accelerated chronic kidney disease. Types 2 and 3 describe acute and chronic kidney disease leading primarily to heart failure, although it is possible that acute coronary syndromes, stroke, and arrhythmias could be CVD outcomes in these forms of CRS. Finally, CRS type 5 describes a simultaneous insult to both heart and kidneys, such as sepsis, where both organs are injured simultaneously. Both blood and urine biomarkers are reviewed in this paper and offer a considerable opportunity to enhance the understanding of the pathophysiology and known epidemiology of these recently defined syndromes.

A novel polyherbal formulation containing thymoquinone attenuates carbon tetrachloride-induced hepatorenal injury in a rat model

Objective:To evaluate a novel polyherbal formulation(BSVT)containing the standardized extracts from the leaves of Boerhavia diffusa,Solidago virgaurea,Vitex negundo,and thymoquinone in CCl4 induced hepatorenal toxicity in rats.Methods:A total of 36 rats were divided into six groups including normal control,CCl4(2 mL/kg,i.p.),CCl4(2 mL/kg,i.p.)+Cystone?(750 mg/kg p.o.),CCl4(2 mL/kg,i.p.)+BSVT(25 mg/kg,p.o.),CCl4(2 mL/kg,i.p.)+BSVT(50 mg/kg,p.o.),and CCl4(2 mL/kg,i.p.)+BSVT(100 mg/kg,p.o.).All treatments were given for four weeks.Serum levels of aspartate transaminase,alanine transaminase,alkaline phosphatase,cholesterol,total protein,serum urea,blood urea nitrogen and creatinine were assessed.Superoxide dismutase,malondialdehyde,and glutathione peroxidase were evaluated in tissue homogenate.The histopathological study of liver and kidney tissues was also done.Results:Aspartate transaminase,alanine transaminase,alkaline phosphatase,cholesterol,serum urea,blood urea nitrogen and creatinine were significantly elevated(P<0.001)while total protein was considerably reduced in the CCl4 group as compared to the normal control(P<0.001),which indicated hepatorenal toxicity.In addition,superoxide dismutase and glutathione peroxidase activities were significantly decreased(P<0.001)while malondialdehyde levels were increased markedly(P<0.001).Treatment with BSVT formulation recovered these parameters towards a normal level in a dose-dependent manner.Conclusions:BSVT formulation ameliorates the hepatorenal toxicity in a dose-dependent manner.Furthermore,clinical studies are required to confirm its efficacy.

A system dynamics model for billion trees tsunami afforestation project of Khyber Pakhtunkhwa in Pakistan:Model application to afforestation activities

As part of the global effort to plant billion trees,an afforestation project is launched in Pakistan in Khyber Pakhtunkhwa(KP)province to conserve existing forests and to increase area under forest cover.The present study is designed to build a Systems'model by incorporating major activities of the Billion Tree Tsunami Afforestation Project(BTTAP)with special focus on afforestation activities to estimate the growth in forest area of KP.Availability of complete dataset was a challenge.To fix the model,the raw data taken from the project office has been utilized.Planning Commission Form 1-Phase I&II helped us with additional information.We relied on the data available for one and half period of the project as rest of the data is subject to the completion of the project.Our results show that the project target to enhance area under forest differs from the target to afforest area under the project.The system dynamics'model projection shows that the forest area of KP would be 23.59 million hectares at the end of the BTTA project,thus having an increase of 3.29%instead of 2%that has been initially proposed.However,the results show that the progress to meet the target in some afforestation classes is slow as compared to other categories.Farm forestry,plantation on communal lands and owners'plantation need special focus of the authority.Deforestation would affect 0.02 million hectares area of the project.The model under study may be used as a reference model that can be replicated to other areas where billion tree campaigns are going on.

Viral hepatitis in Pakistan:challenges and priorities

Hepatitis B and C are big health issues worldwide as more than 400 million people arc suffering from chronic hepatitis B and C which result in more than 1.4 million deaths each year.According to a study done by Pakistan Medical Research Council in 2007-08,7.6%Pakistani population suffered with hepatitis B and C.with around 4.8%with hepatitis C only.Government of Pakistan has taken different initiatives like vaccination,patient safety,blood screening,education and awareness about disease but still there is high prevalence of hepatitis in Pakistan.According to some studies injecting drug users have the highest prevalence of hepatilis B and C in the country.The follow-up studies and documentation of hepatitis patients was not very good which need to be improved.There is no recent large scale study on risk factors and prevalence of hepatitis B and C in Pakistan so it should be done on an urgent basis.If government set up regional laboratories for prevalence study and also a central institute for hepatitis research and treatment,the disease could be prevented in better and proper way.The treatment of hepatitis is very costly and a developing country like Pakistan cannot afford such high costs.Therefore more focus should be on preventive measures.

Eslicarbazepine acetate:A therapeutic agent of paramount importance in acute anticonvulsant therapy

Eslicarbazepine acetate (ESL) is a new, once daily, orally administered, third generation antiepileptic drug which is indicated in the treatment of partial-onset seizures. ESL is known to exert it's anticonvulsant effect by blocking the voltage-gated sodium channels. Several clinical trials and pharmacological studies have revealed that seizure control was better with ESL monotherapy (1 200 or 1 600 mg once daily) following a switch from other antiepileptic drugs in comparison with pseudo-placebo patients. The studies have indicated the ESL to be well tolerated and produced only mild to moderate emergent adverse events with the therapy. Being a dibenzazepine family member, structure and chemistry of ESL resembles more or less to carbamazepine and oxcarbazepine. ESL differs structurally from carbamazepine and oxcarbazepine at the 10, 11 position of dibenazepine nucleus. This molecular variation results in differences in metabolism and thus helps to prevent the formation of toxic epoxide metabolites. ESL following oral administration is rapidly metabolised to active metabolite namely S-licarbazepine which is responsible for its pharmacological activity. ESL exhibits acceptable pharmacokinetic profile and shows insignificant drug-drug interactions. In phase III clinical program, ESL was found to be efficacious and well tolerated in adult patients with partial onset seizures previously not controlled with treatment with one or two other antiepileptic drugs.

Theoretical approach to study the formation of C2H4O2 isomers in interstellar medium through reaction between interstellar formaldehyde molecules

The three isomers of C2H4O2,viz.,glycolaldehyde(HCOCH2 OH),acetic acid(CH3 COOH)and methyl formate(HCOOCH3),have been detected in copious amounts in the interstellar medium(ISM).The possibility for formation of these molecules through interstellar formaldehyde(HCHO)has been explored by using the quantum chemical approach described by density functional theory(DFT)and second order Moller-Plesset perturbation(MP2)theory with a 6–311 G(d,p)basis set in the gas phase as well as in icy grains.The associated molecule-molecule interactions have been discussed to study the formation of isomers of C2H4O2 in ISM.The reactions of two formaldehyde molecules exhibit a considerable potential barrier but due to quantum tunneling,these reactions could be possible in ISM.The chemical pathway is exothermic,which gives rise to a high probability for the formation of all three isomers,viz.glycolaldehyde,methyl formate and acetic acid,in interstellar space.Anharmonic rotational vibration,centrifugal distortion constants and coupling constants are also calculated and results suggest that the vibrations are harmonic in nature.

Response of Yield and Related Attributes of Upland Cotton to Weather Variables

Cotton growth and development is effected by various ecological issues like temperature fluctuations, distribution and quantity of rainfall, relative humidity and winds which are the climate change attributes. A field experiment was carried out to find out the response of cotton to weather variables in terms of total variation in yield and quality. The effect of planting times and thermal temperatures (cumulative heat units) on yield of 4 cotton cultivars viz;CIM-600, CIM-616, CIM-622 & CRIS-641 was evaluated. Plants were sown on 6 planting times during the year 2015-2016 and 2016-2017 in an experiment conducted in randomized complete block design having three replications. Cotton cultivars depicted significant variances for number of bolls plant-1, boll weight and seed cotton yield. The cultivar CIM-616 depicted the highest seed cotton yield of 2083.60 kg·ha-1 on interpretation of highest bolls and boll weight. Maximum seed cotton yield was noted in planting time from 1st April to 15th April whereas early and late planting decreases the seed cotton yield on account of less accretion of cumulative heat units. Regression analysis depicted that rise of one unit (15 days) from early to optimal date (15th March to 15th April) enhanced the seed cotton yield by 93.76 kg·ha-1 (y = -93.764x2 + 521.04x + 1364). Delayed planting also reduces the seed cotton yield with the same ratio. It is therefore established that cotton must be cultivated from 1st April to 1st May to harvest good production in this type of climate.

Luminous composite ultrathin films of CdTe quantum dots/silk fibroin co-assembled with layered doubled hydroxide:Enhanced photoluminescence and biosensor application

Quantum dots(QDs)luminescent films are extensively applied to optoelectronics and optical devices.However,QDs aggregation results in the quenching of their fluorescence property which limits their practical applications to a greater extent.In order to resolve this issue,3-mercaptopropionic acid(3-MPA)functionalized Cadmium Tellurium(CdTe)QDs were stabilized by silk fibroin(SB)and coassembled with layered doubled hydroxide(LDH)to form(QDs@SF/LDH)_(n)ultrathin films(UTFs)via the layer-by-layer(LBL)technique.UV-Vis absorption and fluorescence spectroscopy showed a stepwise and normal growth of the films upon increasing the number of deposition cycles.XRD and AFM studies confirmed the formation of a periodic layered structure and regular surface morphology of the thin films.As compared to(CdTe QDs/LDH)_(n)UTFs,the(CdTe QDs@SF/LDH)_(n)UTFs displayed fluorescence enhancement and longer fluorescent lifetime,both in solid states and aqueous solutions.Furthermore compared with the solution state,the fluorescence enhancement of SF-RC and SF-β are,respectively,7 times and 17 times in the(CdTe QDs@SF/LDH)_(n)UTFs,indicating that the LDH nanosheets favor the fluorescence enhancement effect on the CdTe QDs@SF.The fabricated materials displayed fluorescence response to a biological molecule such as immune globulin,lgG.Thus,the(CdTe QDs@SF/LDH)_(n)UTFs has a potential to be used as biosensor.

Are developing countries prepared to face Ebola-like outbreaks?

Ebola virus disease has caused havoc in West Africa,with 11,162deaths and more than 27,181 cases(as of May 31,2015)being reported since the virus emerged in early2014 in Guinea.The maximum number of cases has been reported in Sierra Leone(12,827),while most of the reported deaths have occurred in Liberia(4,806),according to the Center for Disease Control

Electrospinning:An emerging technology to construct polymer-based nanofibrous scaffolds for diabetic wound healing

A chronic wound in diabetic patients is a major public health concern withsocioeconomic and clinical manifestations.The underlying medical condition of diabeticpatients deteriorates the wound through physiological,metabolic,molecular,and cellularpathologies.Consequently,a wound enters a vicious pathological inflammatory cycle.Many therapeutic approaches are in practice to manage diabetic wounds hence ensuringthe regeneration process.Polymer-based biomaterials have come up with hightherapeutic promises.Many efforts have been devoted,over the years,to build aneffective wound healing material using polymers.The electrospinning technique,although not new,has turned out to be one of the most effective strategies in buildingwound healing biomaterials due to the special structural advantages of electrospunnanofibers over the other formulations.In this review,careful integration of allelectrospinning approaches has been presented which will not only give an insight intothe current updates but also be helpful in the development of new therapeutic materialconsidering pathophysiological conditions of a diabetic wound.

Chiral symmetry restoration and deconfinement in the contact interaction model of quarks with parallel electric and magnetic fields

We study the impact of steady,homogeneous,and external parallel electric and magnetic field strengths(eE||eB)on the chiral symmetry breaking-restoration and confinement-deconfinement phase transition.We also sketch the phase diagram of quantum chromodynamics(QCD)at a finite temperature T and in the presence of background fields.The unified formalism for this study is based on the Schwinger-Dyson equations,symmetry preserving vector-vector contact interaction model of quarks,and an optimal time regularization scheme.At T=0,in the purely magnetic case(i.e.,eE→0),we observe the well-known magnetic catalysis effect.However,in a pure electric field background(eB→0),the electric field tends to restore the chiral symmetry and deconfinement above the pseudo-critical electric field eE^(x,C)_(c).In the presence of both eE and eB,we determine the magnetic catalysis effect in the particular region where eB dominates over eE,whereas we observe the chiral inhibition(or electric chiral rotation)effect when eE overshadows eB.At finite T,in the pure electric field case,the phenomenon of inverse electric catalysis appears to exist in the proposed model.Conversely,for a pure magnetic field background,we observe the magnetic catalysis effect in the mean-field approximation and inverse magnetic catalysis with eB-dependent coupling.The combined effects of eE and eB on the pseudo-critical T^(x,C)_(c)yields an inverse electromagnetic catalysis,with and without an eB-dependent effective coupling of the model.The findings of this study agree well with the already predicted results obtained via lattice simulations and other reliable effective models of QCD.

Color-flavor dependence of the Nambu-Jona-Lasinio model and QCD phase diagram

We study the dynamical chiral symmetry breaking/restoration for various numbers of light quarks flavors N_(f) and colors N_(c) using the Nambu-Jona-Lasinio(NJL) model of quarks in the Schwinger-Dyson equation framework,dressed with a color-flavor dependence of effective coupling.For fixed N_(f)=2 and varying N_(c),we observe that the dynamical chiral symmetry is broken when N_(c) exceeds its critical value N_(c)^(c)≈2.2.For a fixed N_(c)=3 and varying N_(f),we observe that the dynamical chiral symmetry is restored when Nf reaches its critical value N_r^(c)≈8.Strong interplay is observed between N_(c) and N_(f),i.e.,larger values of N_(c) tend to strengthen the dynamical generated quark mass and quark-antiquark condensate,while higher values of N_(f) suppress both parameters.We further sketch the quantum chromodynamics(QCD) phase diagram at a finite temperature T and quark chemical potential μ for various N_(c) and N_(f).At finite T and μ,we observe that the critical number of colors N_(c)^(c) is enhanced,whereas the critical number of flavors N_(f)^(c) is suppressed as T and μ increase.Consequently,the critical temperature T_(c),μ_(c),and co-ordinates of the critical endpoint(T_(c)^(E),μ_(c)^(E)) in the QCD phase diagram are enhanced as N_(c) increases and suppressed when N_(f) increases.Our findings agree with the lattice QCD and Schwinger-Dyson equations predictions.

Chemical modification of acetaminophen：PASS assisted in vivo antiinflammatory activity of chalcones,flavanones and Schiff bases

In the present study,synthetic chalcones,flavanones and Schiff bases were prepared starting from paraceamol,and evaluated their anticipated anti-inflammatory activity.Chalcones were synthesized by reacting 3-acetyl-4-hydroxy acetanilide and aromatic aldehydes in alcoholic potassium hydroxide(KOH) solution under Claisen-Schmidt condensation conditions.The chalcones were cyclized in the presence of piperidine in isoamyl alcohol to obtain flavonone derivatives.Schiff bases were synthesized by condensing 3-acetyl-4-hydroxy anilines with aromatic aldehydes in the presence of HCl.These Schiff bases were further reacted with other aromatic aldehydes in alcoholic KOH solution.PASS cheminformatics software was used to predict the anti-inflammatory activity of synthesized compounds.PASS software predicted that chalcone-based Schiff bases 6a–d contained structural features that can exhibit anti-inflammatory activity.All the prepared derivatives of acetaminophen exhibited moderate to excellent in vivo anti-inflammatory activity in carrageenan-induced edema in rat paw.All the Schiff bases coupled chalcones showed good anti-inflammatory activity compared with the reference drug,diclofenac.Further evaluation of their therapeutic potential and safety profile is required in the future study.

HIV awareness in Pakistan:A survey-based study

Objective:To know the awareness level of Pakistani population about AIDS.Methods:An online survey was conducted in Pakistan with the help of a questionnaire formulated by experts to record the awareness level of common people about HIV infection.The responses were collected and screened by the team of National Academy of Young Scientists,Pakistan.Results:Among the 580 participants of the survey,majorities were male,in the age group of 20-30 years and were living in urban areas.More than 80%of responders did not ever screen themselves for HIV and close to 40%were not aware that where to go for screening.Although,majority of the respondents knew about the nature of disease,they were not fully aware about different tests,treatment,duration of infection and vaccination.According to participants,television and internet were major source of information about AIDS and this disease can be prevented in Pakistan through public awareness.Conclusions:Since majority of the respondents were not fully aware about the disease and its mode of transmission,there should be print and electronic media campaigns as well as workshops and seminars to educate the common public.In addition,a national level prevalence study will be very helpful to know the exact prevalence of HIV in Pakistan and its major routes of transmission.

A Methodology for Development of Software Composite-Metrics for Program Control-Flow Structure

This paper reports on a pioneer effort for the establishment of a software composite metric with key capability of distinguishing among different structures. As a part of this effort most of the previously proposed program control-flow complexity metrics are evaluated. It is observed that most of these metrics are inherently limited in distinguishing capability. However, the concept of composite metrics is potentially useful for the development of a practical metrics. This paper presents a methodology for the develop- ment of a practical composite metric using statistical techniques. The proposed metric differs from all previous metrics in 2 ways: (1) It is based on an overall structural analysis of a given program in deeper and broader context. It captures various structural measurements taken from all existing structural levels; (2) It unifies a set of 19 important structural metrics. The compositing model of these metrics is based on statistical techniques rather than on an arbitrary method. Experinces with the pro- posed metric clearly indicate that it distinguishes different structures better than the previous metrics.