At times, other people’s belief systems, including that of the buy Crizotinib survivors themselves, can be a barrier to accepting the death and a deterrent to talking about it. When coping

with a loss, people often turn to religion for comfort and guidance. A challenge for some survivors is that several religions impose shameful restrictions on the grief rituals for those who have been bereaved by suicide. Suicide survivors face Inhibitors,research,lifescience,medical additional logistical barriers when handling the deceased’s business after a suicide, as most insurance policies even have clauses with built-in stigma.49 Despite alarmingly high rates of suicides in the United States military, it was only until very recently (July 6, 2011) that the United States Government began to honorably acknowledge the bereaved after a military suicide, as is done for other deaths that occur in combat zones. For many people, talking about their loved ones is vital for their recovery from their loss. The stigma of suicide poses a barrier to the healing process.37 Inhibitors,research,lifescience,medical Trauma Survivors of suicide are more likely than other bereaved individuals to develop symptoms of PTSD.50 The majority of suicide methods involve considerable bodily damage. Occasionally,

survivors are witnesses to the final act, or the first to discover the dead body. Those left to find Inhibitors,research,lifescience,medical the deceased’s body struggle to get the gruesome images of out of their minds.51 In such circumstances, Inhibitors,research,lifescience,medical traumatic distress, marked by

fear, horror, vulnerability, and disintegration of cognitive assumptions ensues. One survivor told us the poignant story of her boyfriend, who immediately after a breakup, climbed to a nearby bridge and leaped to his death while she looked on in horror. Not unexpectedly, her grief was replete with such trauma symptoms as preoccupation with reminders, terror-filled recollections, avoidance of high places, and other reminders. After a death by suicide, themes Inhibitors,research,lifescience,medical of violence, victimization, and volition (ie, the choice of death over life, as in the case of suicide) are common and may be intermixed with other aspects of grief. Disbelief, despair, anxiety symptoms, preoccupation with the deceased and the circumstances of the death, withdrawal, hyper isothipendyl arousal, and dysphoria are more intense and more prolonged than they are under nontraumatic circumstances.52 Suicide risk in survivors Suicide and mental illness runs in families, likely a result of both heritability and environmental factors.7,8 Survivors of suicide may be left to struggle with their own suicidal ideation, while seeing that the deceased escaped the anguish and put an end to their suffering. Despite the fact that the suicide bereaved intimately understand the intense pain and suffering experienced by all those who survive a suicide loss, survivors are at higher risk themselves for suicidal ideation and behavior than are other bereaved individuals.

“
“Epilepsy is the most common neurological disorder characterized by recurrent spontaneous seizures Selleckchem RG-7204 affecting 1–2% of the population worldwide.1 The most underlying mechanism in the Libraries development and progression of epilepsy and several other neurological disorders is oxidative stress.2 Oxidative stress is caused by excessive production of reactive oxygen species such as hydroxyl, superoxide anion radical, nitric oxide and hydrogen peroxide.3 There are so many drugs available to treat epilepsy but none of them are free from side effects

such as depression, ischemia, impaired cognition, motor disability and etc.4 Among all, depression is the common side effect produced by most of the antiepileptic drugs and that remains untreated.5 It has been observed that seizure activity during epilepsy increases the amount of free radicals and decreases the antioxidant defense

mechanism in Sorafenib the brain which further induce the oxidative stress.3 The extract obtained from plants of the genus Leucas display a wide range of pharmacological activities such as antioxidant, hepatoprotective, antiinflammatory, antidiabetic, antimicrobial, antidiarroheal and antinociceptive activity. 6, 7, 8 and 9 No research or scientific work has been done on Leucas lanata, therefore the present study is aimed at exploring the potential of free radical scavenging activity along with its capability to treat epilepsy. 1, 1-Diphenyl-2-picryl hydrazyl, 2-thiobarbituric acid, 1, 1, 3, 3-tetramethoxy propane and pentylenetetrazole were obtained from Sigma–Aldrich, St Louis, MO, United States. Phenazine methosulphate, nitroblue tetrazolium and sulfanilamide were purchased from NR chemicals Pvt Ltd, Mumbai, India. Sodium nitroprusside was obtained from HiMedia Laboratories Pvt Ltd, Mumbai, India. 2-Deoxy-d-ribose and reduced nicotinamide adenine dinucleotide were obtained from Sisco Research Laboratories Pvt. Ltd, Mumbai, India and all other reagents and solvents used

were of analytical grade and obtained from various other commercial sources. The whole plant of L. lanata was collected from Tirulmala hills, Andhra Pradesh, India. L. lanata was authenticated with vochure number 1798. 500 g of air dried and powdered L. Levetiracetam lanata was first defatted with petroleum ether at room temperature for 72 h. The defatted material was extracted with 95% ethanol at room temperature for 72 h. The resultant ethanolic extract was concentrated under reduced pressure at room temperature using rotary vacuum evaporator. Ethanolic extract of L. lanata was subjected for preliminary phytochemical screening to determine the presence of carbohydrate, alkaloid, amino acid, flavonoid, phenolic substance, steroid, protein, saponin and tannin. 10 0.5 ml of ethanolic extract was estimated for total phenolic and flavonoids contents by using UV spectrophotometric method.

A criticism of the study is the fact that allocation of the patients was not random, which may present potential biases. A large-scale randomized trial for comparison of minilaparotomy and laparoscopic rectal cancer surgeries is needed. Careful patient selection is also crucial. Acknowledgements Disclosure: The authors have no conflicts of interest.
Signet Inhibitors,research,lifescience,medical ring cell carcinoma (SRCC) of colon and mucinous adenocarcinoma (MCC) of colon are rare histologic subtypes of adenocarcinoma of colon accounting for approximately 0.5-1 percent and 15-20 percent of all adenocarcinomas of colon respectively (1). Signet ring cell cancers are most Sotrastaurin commonly seen

in the stomach (95%) and occasionally found in colon, rectum, ovary, peritoneum and gallbladder (2). It is characterized by specific morphologic appearance of abundant intracytoplasmic mucin

pushing nucleus to the periphery giving it a signet ring cell appearance. SRCC is similar to MCC in possessing abundant mucin. The World Health Organization classification of tumors has a specific criteria for Inhibitors,research,lifescience,medical diagnosis of these sub types–SRCC is defined as presence of more than 50 percent of signet cells and MCC is defined as presence of more than 50 percent of mucin component (3). Previous studies Inhibitors,research,lifescience,medical have shown that SRCC often presents at young age, in advanced stage, with more peritoneal involvement and has poor prognosis (4,5). However, majority of these studies are single institution based including Inhibitors,research,lifescience,medical small number of patients. Because of the rarity of the disease, clinico-pathological features and prognosis has not been well understood and there have been very few studies comparing SRCC with MCC and non-mucinous adenocarcinoma (NMCC) of colon. Hence we conducted

a retrospective study on the large nationwide veteran population to understand the clinicopathological features and the survival outcomes of SRCC, MCC and NMCC. Methods Data source The study was approved by the local Institutional Review Board. Data for this study was obtained by accessing the Veteran’s Affairs Central Cancer Registry (VACCR) database. VACCR is a population-based registry sponsored by Inhibitors,research,lifescience,medical the Veteran’s Affairs Healthcare system that contains information from patients diagnosed and/or treated at all 143 Veterans Affairs (VA) medical centers. Each case report adheres to the standards established Calpain by the American College of Surgeons’ Commission on Cancer Facility Oncology Registry Data Standards for data collection and definitions and must pass North American Association of Central Cancer Registry electronic quality assurance edits before being merged/consolidated into the master database. Study population A total of 36,260 Veteran’s diagnosed with colon cancer between January 1995 and December 2008 were identified from the VACCR database. Of which 26,669 were NMCC patients, 2,443 were MCC patients, and 206 were SRCC patients and 6,942 were other histology’s.

42 Neurological involvement accounts for up to 5% of extrapulmonary TB, especially in children and/or immunodeficient patients.43 There are different reports about the incidence of stroke in neurotuberculosis. Dastur et al.44 reported cerebral infarction in 41% of 100 autopsied brain. In post-computer tomography era the reported incidence is between 28 to 38% without any prominent sex Inhibitors,research,lifescience,medical dominance.45,46 The highest rate of vascular infarction during TBM, diagnosed by MRI, is reported more than two thirds of the patients.47 Ninety-two percent of the involved arteries were in the anterior

cerebral circulation (carotid system).43,46 Lenticulostriate arteries of both middle and anterior cerebral arteries are mostly involved. Large infarctions are mainly due to middle cerebral

artery involvement, and brainstem infarction is due to occlusion of penetrating Inhibitors,research,lifescience,medical branches of basilar artery.46,48 A recent report showed that the hazard ratio of ischemic stroke for tuberculosis patients (not meningeal or CNS tuberculosis) was 1.52-times (95% CI, 1.21-1.91; P<0.001) higher than that for control group.49 The current guidelines for treatment Inhibitors,research,lifescience,medical are based on the advances of the recent chemotherapeutic achievement of anti-TB drugs,50 and medical or surgical management for ischemic strokes. Early treatment is mandatory, and delayed treatment is associated with a higher rate of mortality and morbidity. Inhibitors,research,lifescience,medical Dexamethasone appears useful as an adjunctive treatment, especially in patients with severe tuberculous meningitis. Syphilis Syphilis is the great masquerader. Two types of symptomatic neurosyphilis, paranchymatous and meningovascular have been described.42,51

About 5% of untreated syphilitic patients will develop neurosyphilis,52 especially in young adults. Two different types of vascular pathology have been described in meningovascular syphilis. Hübner arteritis, which Inhibitors,research,lifescience,medical had been described since long times ago, is the most common type and involves the large and medium sized vessels. The other pathology is Nissl’s endarteritis characterized by intimal and adventitial proliferation, mainly on small vessels.1 Mostly middle almost cerebral artery is affected.41 Different types of atherosclerotic plaques have been reported, but it should be defined that the presence of such lesions in neurosyphilitic patients does not imply a Selleck AZD2014 cause-and-effect relationship.53 Neurological manifestations consist of motor and sensory impairment, and relate to the size and location of the lesion. Syphilis can affect any part of the neuraxis. A high index of clinical suspicion requires early diagnosis and treatment of neurosyphilis, particularly in patients with promiscuous sexual activity.54 However, in HIV positive patients, the diagnosis and treatment of neurosyphilis is challenging.

2005], thus it follows that lithium potentially exerts a therapeutic effect by affecting cell signalling as a result of IMPase inhibition, and subsequent reduction

of elevated inositol and phosphatidylinositol levels [Haimovich et al. 2012]. This notion is further supported by the fact that lithium is an uncompetitive inhibitor of IMPase [Berridge and Irvine, 1989], thus the level of inhibition increases at high substrate concentrations; since myo-inositol levels are higher in bipolar patients [Silverstone et al. 2005], the level of inhibition Inhibitors,research,lifescience,medical is increased in these individuals, potentially explaining why lithium treatment is effective in bipolar disorders Inhibitors,research,lifescience,medical but not in comparative normal subjects [Berridge and Irvine, 1989]. Despite the extensive evidence in support of inositol depletion as a viable explanation of lithium’s pharmacodynamic actions, other click here observations have been inconsistent and often contradictory [Marmol, 2008]. Shaltiel and colleagues, for example, found reduced IMPase activity in lymphocyte-derived Inhibitors,research,lifescience,medical cell lines of bipolar patients [Shaltiel et al. 2001]. A lack of novel blood–brain barrier penetrant

IMPase inhibitors currently limits evaluating the precise biochemical and therapeutic effects of lithium-induced inositol depletion [Gould and Manji, 2005]. The mechanism by which lithium exerts its effects on the PI signalling pathway is still unclear, and it remains possible, for example, that a decrease in intracellular myo-inositol is only the first

stage of Inhibitors,research,lifescience,medical action, initiating a cascade of secondary changes in the PKC signalling pathway and gene expression [Agam et al. 2002; Manji and Chen, 2002], that are ultimately associated with lithium’s Inhibitors,research,lifescience,medical therapeutic efficacy. Further research, and the development of appropriate pharmacological agents, are therefore still required, to enable results of greater consistency, and to determine the exact mechanism by which lithium-induced inositol depletion has a therapeutic effect in patients with mood disorders. Glycogen synthase kinase 3 The ubiquitous serine/threonine protein kinase glycogen synthase kinase 3 (GSK3), offers another potential target for lithium. GSK3 is a critical CYTH4 downstream regulator of diverse signalling pathways [Zhang et al. 2003; Chiu and Chuang, 2010], and has a key role in the regulation of a number of cell functions, including insulin receptor signalling, the specification of cell fates during embryonic development, immunity and inflammation responses and neurotransmission [Cohen and Frame, 2001; Kaidanovich-Beilin and Woodgett, 2011].

13, 14, 15 and 16 In the present study the binding interactions of some of the 3,4-heteroannelated quinolin-2-ones with DNA Gyrase as well as their antibacterial activity has been reported. These compounds are assumed to bind to inhibit the DNA Gyrase 2 of S. aureus in a similar fashion as ciprofloxacin does, since the compounds share structural similarity with Ciprofloxacin. The potential compounds are identified and their antibacterial activity is evaluated against S. aureus and Escherichia coli and

reported here. To study the MK-1775 research buy extent of interaction of the synthesized 3,4-heteroannelated quinolin-2-ones with the DNA Gyrase of S. aureus, the compounds were docked to the protein using the GOLD 3.2 (Genetic Optimization for inhibitors ligand Docking) software. The docked poses of each ligand were analyzed and fitness Scores are calculated with Silver. Screening of antibacterial activity of title compounds was done by adopting disc diffusion method as described by Cruickshank et al (1975)17 using S. aureus

Gram +ve (Oxford strain) and E. coli Gram −ve (NCTC 10148). The synthesized compounds were constructed and prepared for docking using the Ligprep Protocol of Maestro. Ligand minimization was done using OPLS 2005 Force field. The synthesized compounds were constructed and prepared for docking using the Ligprep Protocol of Maestro. A high resolution (2.1 Å) crystal structure of S. aureus DNA Gyrase is selected and docked using GOLD 3.2. The GOLD find more fitness function is made up of four components: protein–ligand hydrogen bond energy, protein–ligand Vander Waals energy, ligand internal vdw energy and ligand torsional strain energy and the fitness score is taken as the negative of the sum of the component energy terms. The docked poses of each ligand were visualized and the interactions were analyzed with Silver. The best Fitness

Scores for each ligand are tabulated along with the details of H-bonds and other interactions in Table 1. The binding poses of the ligands to the proteins are shown in Fig. 1. Compound 1b has the highest fitness score of 51.23. Compounds 1a, 1c, 2d and 2j also showed good fitness scores Suplatast tosilate next to 1b. 11 compounds show good fitness score values as compared to Ciprofloxacin. Screening of antibacterial activity of title compounds was done by adopting disc diffusion method as described by Cruickshank et al (1975).17 The compounds were dissolved in appropriate solvents (AR grade) and Whatman No.1 filter paper discs of 6 mm diameter were prepared with various concentrations of test compounds ranging from 200 to 3.125 μg/disc. The test organisms used were S. aureus Gram +ve (Oxford strain) and E. coli Gram −ve (NCTC 10148).

Novel treatment strategies, including NMDA selleck chemicals llc receptor antagonists, could act via reversal of these synaptic deficits. Stress and depression cause neuronal atrophy and loss: circuit-specific

effects Among the findings of altered brain structure and function in depression, the most consistent is reduced volume of the PFC and hippocampus (Figure 1).11,12 Reduced volume Inhibitors,research,lifescience,medical is inversely correlated with length of illness, time of treatment, and severity of depression. Postmortem studies also demonstrate reduced neuronal cell body size, atrophy of processes, and a reduction of glia in PFC.13-15 Although ultrastructural studies, such as spine synapse analysis, have been difficult in postmortem tissue, a recent report demonstrates a decrease in the number of synapses in the PFC in a small cohort of depressed subjects.16 Findings in rodent models have extended the human studies, Inhibitors,research,lifescience,medical and confirm that exposure to chronic stress, like depression, causes atrophy and loss of neurons and glia in the PFC and hippocampus, Inhibitors,research,lifescience,medical which could contribute to the decreased volume reported in patients.3,13,17,18 The atrophy of neurons is characterized by a decrease in the number and length of dendrite branches, as well as a decrease in the density of spine synapses.18-20 Figure 1. Chronic stress causes

neuronal atrophy: a decreased number of spine synapses. Basic research studies demonstrate that repeated stress causes atrophy of neurons in the prefrontal cortex and hippocampus of rodents. Shown on the left is a diagram of a segment … In contrast to the atrophy Inhibitors,research,lifescience,medical observed in PFC and hippocampus, stress causes hypertrophy of neurons in the amygdala, which could contribute to increased emotional valence and anxiety in depression.21 Hypertrophy and increased function of amygdala could

result from atrophy and decreased function Inhibitors,research,lifescience,medical of PFC, as this region provides inhibitory control of amygdala and could thereby contribute to depressive symptoms. Similarly, atrophy and decreased function of PFC neurons could contribute to abnormal function of other aspects of the depression circuit (eg, increased activity of basal ganglia and subcallosal cingulate cortex). Stress decreases neuronal and glial Ketanserin proliferation In addition to decreased neuronal arborization and synapse number, stress also exerts a significant impact on the birth of new neurons and glia. Acute and chronic stress decreases neurogenesis in the dentate gyrus of adult hippocampus.22 There have also been several studies of cell proliferation in the hippocampus of postmortem depressed subjects, although there is no evidence to date of decreased neurogenesis, indicating that loss of neurons does not contribute to depression.23 Rather, these postmortem studies have reported that depressed patients treated with antidepressants have increased levels of newborn cells in the hippocampus.

This is one of the values of GoWell, namely that it looks at how

the effects of interventions can differ depending on a variety of challenging social circumstances; comparisons with stable PD0325901 residential areas will not tell us that. A further challenge lies in engaging residents in the research and thereby obtaining good response rates and representative samples. GoWell has achieved response rates of about 50% over the three waves of data collected so far, which we consider reasonable given the challenges described above combined with police safety campaigns in many of our study areas urging residents not to open their doors to unexpected callers. To help us maintain our response rate we have adopted a number of techniques, including newsletters and neighborhood awareness raising, prize draws and vouchers for participants. Regeneration can be considered a natural experiment (Craig et al., 2012). Researchers have no control over the planning, delivery or allocation of the intervention(s),

which are not neatly contained within a certain period of time, nor necessarily mutually exclusive. Further the residents in study areas may have been exposed to previous urban renewal activities. Guidance for the evaluation of natural experiments states that evaluations are best undertaken when the implementation is ‘immediate’ and the effects are likely to be large and happen soon after the event (e.g. smoking ban legislation) (Craig et al., 2012). Urban regeneration can be thought of as a natural

Paclitaxel experiment but it does not meet these guidelines: it does not happen overnight; effects are not likely to be large or inhibitors immediate. Evaluation of a slow natural experiment raises particular problems with attributing effects and defining controls. When evaluating an intervention whose effects may take many years to be realized it is often not TCL possible to identify control or comparison areas that will not also be exposed to some regeneration activities during that time. Thus it is difficult to disentangle intervention effects from confounding variables. We have tried to address this challenge in a number of ways. First, by comparing experiences of different types of regeneration to look for differential effects and pathways rather than a single ‘intervention’ effect and second, comparing GoWell health and social outcomes with Glasgow-wide data. Across the city, it is possible to identify areas for comparison, which have not had the same extent or mix of interventions as our study areas, but which are comparable in other ways, thus enabling us to tease out and attribute intervention effects using ecological data. Again, this relies upon the careful identification of the nature and extent of regeneration activity in different places. Our approach to the analysis of survey data contributes to the assessment of attribution.

The cause of these changes is unclear. Kidney stone formation is usually due to genetic and environmental factors. Although genetic

factors influence stone risk, changes in the gene pool occur at a slow rate. Therefore, it is unlikely to be the driving force for these trends. Environmental factors are also varied and complex, but their influence is more apparent as changes in these factors occur over much Inhibitors,research,lifescience,medical shorter intervals. We believe that changes in 2 of the most important environmental factors-diet and climate-have the most significant impact on these trends. There is historical evidence of the influence of diet on stone formation. The first documented increase in stone disease occurred during

the 16th century when European Stein-Schneiders (stone cutters) found that their services were Inhibitors,research,lifescience,medical more in demand.32 During this period, there were improvements in food production and corn became a popular food staple.33 The increased consumption of starchy foods derived from corn promoted obesity, currently a known risk factor for stone formation.3,5,34 The impact of agricultural modernization remains today, and is reflected by the epidemic in obesity seen in many countries, especially the United States. The prevalence of obesity has been tracked in the United Selleck Lapatinib States since 1960. Obesity in adults has risen from 14.6% in the 1971 through 1974 time period to 35.2% in Inhibitors,research,lifescience,medical the 2005 through 2006 time period.35 Moreover, a similar trend is present for children, with 11% to 17.8% being in the overweight category in the 2005 through 2006 Inhibitors,research,lifescience,medical time period.35 The consumption of fast foods and high fructose corn syrup preparations has been thought to promote this epidemic. In the United States Inhibitors,research,lifescience,medical alone, the percentage of meals coming from fast-food eateries or restaurants rose from 9.6% to 23.5% during the timeframe of 1977 to 1996.36 These dietary changes have also been reported in many other countries including China, India, Egypt, Russia, and the Philippines. 36–39 High fructose consumption has been demonstrated to be a risk most factor for stone formation.40

Other dietary risk factors for stone formation have been identified. There is strong evidence that diminished fluid and calcium consumption are risk factors.14,41–44 Increased oxalate consumption has also been demonstrated to promote stone formation. 45,46 Epidemiologic studies have demonstrated that increased sodium and animal protein intake have an equivocal impact on stone risk. However, a randomized prospective dietary intervention study demonstrated that reduction of sodium and animal protein and maintenance of normal dietary calcium intake attenuates stone activity in recurrent hypercalciuric stone formers.41 There is evidence that the consumption of animal protein has increased in a number of countries, paralleling the acceleration of stone disease.

Cultured microglial cells also expressed both mRNAs (Fig. 2F). Given the high level of expression of GM-CSFRα-mRNA in the cultured microglia, it is likely that the main source of GM-CSFRα-mRNA in the ventral

midbrain is microglia. On the other hand, DArgic neurons may be the main source of IL-3Rα-mRNA. Figure 2 Expression of receptors Inhibitors,research,lifescience,medical for GM-CSF and IL-3 in the SNpc and primary cultured microglia. (A) BLU9931 mw immunoreactivity of GM-CSFRα was localized to microglial cells (yellow arrowheads) and DArgic neurons (blue arrowheads). Microglial cells were identified … Increased expression of Bcl-xL in DArgic neurons in the SNpc of the cytokine-injected rats Both GM-CSF and IL-3 have been reported to increase the expression of antiapoptotic factors belonging to the Bcl-2 family in isolated neurons (Wen et al. 1998; Huang et al. 2007; Schabitz et al. 2008). Immunohistochemical staining with antibodies to Iba1, TH, and Bcl-xL Inhibitors,research,lifescience,medical revealed that Bcl-xL immunoreactivity was localized to capillary-like Inhibitors,research,lifescience,medical structures (yellow arrowheads) in and around the SNpc in a sham rat

(Fig. 3A). Bcl-xL-immunoreactivity was similarly localized in a saline-injected Parkinsonian rat, although the immunoreactivity was markedly suppressed (Fig. 3B). By contrast, strong Bcl-xL-immunoreactivity was localized to DArgic neurons of a cytokine-injected rat (Fig. 3C, blue arrowheads). Note that the activated morphology of microglia was found in the SNpc, only in the ipsilateral side of the 6-OHDA-treated rats. Furthermore, immunoreactivity at a similar level was observed in DArgic neurons in the contralateral SNpc of the cytokine-injected rat, Inhibitors,research,lifescience,medical where microglia display resting ramified Inhibitors,research,lifescience,medical morphology (Fig. 3D). qRT-PCR showed a significant increase of Bcl-xL-mRNA in the cytokine group (Fig. 3E), and the proapoptotic factor Bax-mRNA did not significantly change among the three groups (Fig. 3F).

In comparison with the mRNA data, Bcl-xL protein was not increased in the cytokine group compared with the sham group. However, the Bcl-xL protein was markedly decreased until in the saline group (Fig. 3G). These data suggest that 6-OHDA administration accelerates degradation of Bcl-xL protein and that the cytokine injection increased the transcription of Bcl-xL mRNA in DArgic neurons. Figure 3 Antiapoptotic factor Bcl-xL expression in the SNpc. (A–D) Representative immunohistochemical data showing expression of Bcl-xL protein in the SNpc of sham, saline, and cytokine group at 1 week after 6-OHDA administrations. Localization of Bcl-xL … Phenotypic changes of microglia in response to the cytokines It has been shown previously that primary cultured rat microglial cells change their morphology in response to GM-CSF and IL-3 (Fujita et al. 1996).