process is initiated by the binding of albumin to a


process is initiated by the binding of albumin to an endothelium surface, 60-kDa glycoprotein (gp60) receptor (albondin), which will then bind with an intracellular protein (caveolin-1) to cell assay result in the invagination of the endothelium membrane to form transcytotic vesicles, the caveolae (9). The caveolae will subsequently move across the cytoplasm Inhibitors,research,lifescience,medical and release the albumin and its conjugated compound into the extracellular space (the peritumoral microenvironment) where the albumin will bind to SPARC (secreted protein acid and rich in cysteine), an extracellular matrix albumin-binding glycoprotein that is structurally and functionally closely related to gp60, and overexpressed in a variety of cancers, including breast cancer, gastric cancer and pancreatic cancer. Inhibitors,research,lifescience,medical Nab-Dorsomorphin solubility paclitaxel (Abraxane®) is a cremophor (CrEL)-free, albumin-bound, nanoparticle formulation of paclitaxel. Its CrEL-free formulation permits nab-paclitaxel to be administered within a shorter infusion period of time (30 minutes) and without the requirement

of routine pre-medications for preventing the hypersensitivity reactions in association with the administration of cremophor solvent-based paclitaxel (10). In preclinical study, the transport of radiolabeled paclitaxel across the endothelial cell monolayer in Inhibitors,research,lifescience,medical vitro, and intratumor paclitaxel accumulation after equal doses of paclitaxel in vivo were both significantly enhanced by 4.2-folds (P < 0.0001) and 33% (P < 0.0001), respectively, for nab-paclitaxel as compared with CrEL-paclitaxel with an increase 4.2 folds. In addition, Inhibitors,research,lifescience,medical endothelial transcytosis was completely inhibited by inhibitor of gp60/caveolar transport, methyl ß-cyclodextrin (11). These observations supported that gp60-mediated

transcytosis and SPARC-aided sequestration may be an important biological Inhibitors,research,lifescience,medical pathway to target tumor cells by novel albumin-bound therapeutics. In a phase I trial, the maximum tolerated dose (MTD) of intravenous injection nab-paclitaxel monotherapy, every 3 weeks in 19 patients with standard therapy-failure solid tumors was 300 mg/m2. No acute hypersensitivity reactions were observed. The most frequent toxicities were myelo-suppression, sensory neuropathy, nausea/vomiting, arthralgia and alopecia (12). The drug has subsequently approved for the Entinostat treatment of metastatic breast cancer after failure of combination chemotherapy or relapse within 6 months of adjuvant chemotherapy. The commonly used dose/schedule was 260 mg/m2, 30-min intravenous injection, every 3 weeks. Because SPARC is frequently overexpressed and associated with poor clinical outcomes in pancreatic cancer, Von Hoff et al conducted a phase I/II study to evaluate the MTD of weekly nab-paclitaxel (100 – 150 mg/m2/week) in combination with gemcitabine (1000 mg/m2/week), and the therapeutic efficacies of the regimen. Both agents were given on day 1, 8, and 15 every 28 days ((13)).

Minor abnormalities such as I degree atrio

Minor abnormalities such as I degree atrioventricular block, non-specific ST-T wave abnormalities, sinus tachycardia and premature atrial contractions were considered normal. San Francisco Syncope Rule Study: Presence of non-sinus rhythm and any new changes in comparison to the previous electrocardiogram was considered abnormal. If no old electrocardiogram is available then any changes present are sufficient to classify the electrocardiogram as abnormal. STePS (Short-Term Prognosis in Syncope) Study: ECG was defined as abnormal if any of the following were Inhibitors,research,lifescience,medical present: 1) atrial fibrillation

or tachycardia; 2) sinus pause Inhibitors,research,lifescience,medical ≥2 seconds; 3) sinus bradycardia with heart rate ranging between 35 and 45 beats/min; 4) conduction disorders (i.e., bundle branch block, second-degree Mobitz I atrioventricular block); 5) ECG signs of previous myocardial infarction or ventricular hypertrophy;

and 6) multiple premature Inhibitors,research,lifescience,medical ventricular beats. EGSYS (Evaluation of Guidelines in Syncope Study): The abnormalities that classified the ECG as abnormal in the EGSYS study were: Sinus bradycardia, atrioventricular block greater than first degree, bundle branch block, acute or old myocardial infarction, supraventricular or ventricular

tachycardia, left or right ventricular hypertrophy, ventricular pre-excitation, long QT and Brugada Inhibitors,research,lifescience,medical pattern. Sun et al. [47]: ECG was considered abnormal if any of the following were present: non-sinus rhythm, sinus rhythm with Inhibitors,research,lifescience,medical pulse rate<40 beats/min, Q/ST/T changes consistent with acute or chronic ischemia, abnormal conduction intervals (QRS >0.1 milliseconds, QTc >450 milliseconds), left or right ventricular hypertrophy, left axis deviation, and bundle branch block. Professional society guidelines Dacomitinib There are also three pertinent clinical guidelines from professional societies for risk stratification of ED syncope patients [1,14,48]. The European Society of Cardiology published guidelines for admission in 2001, 2004 and recently updated them in 2009 (European Society of Cardiology – Guidelines for Admission of Syncope Patients) [1,49,50]. Studies validating these guidelines either found no effect or were of poor methodological quality [51,52]. European Society of Cardiology – Guidelines for Admission of Syncope Patients The European Society of Cardiology 2001 and 2004 guidelines for admission are similar and recommend admission either for diagnosis or treatment and are as follows: 1.

Schematic representation of functionalized CNTs with various mole

Schematic representation of functionalized CNTs with various molecules is given

in Figure 4. The functionalization can be divided into two main subcategories: noncovalent functionalization and covalent functionalization. Figure 4 Schematic illustration of functionalization of CNTs with various molecules: (a) Prakash et al. [18], (b) Xiao et al. [78], (c) Xu et al. [70], (d) Gomez-Gualdron et al. [64], (e) Bianco et Inhibitors,research,lifescience,medical al. [79], (f) Jiang et al. [80], (g) Williams et al. [81], and … 3.1. Covalent Functionalization Covalent functionalization of CNTs with the therapeutically kinase inhibitor Axitinib active molecule or the biocompatible surfactants is governed by the oxidation of CNTs using strong acids (conc. H2SO4 or conc. HNO3) which generates substitutable hydrophilic functional groups such as COOH and OH on the CNTs which then further undergo into the chemical Inhibitors,research,lifescience,medical reactions

such Inhibitors,research,lifescience,medical as esterification, amidation, chlorination, bromination, hydrogenation, and Diel’s-Alder reaction. In order to get functionalized with these active molecules, CNTs allow side-wall covalent attachment of functional groups by the inhibitor licensed addition of radicals, nucleophilic carbenes, nitrenes, nucleophilic cyclopropanation, and electrophiles [79, 83, 84]. The method of oxidation results in the opening of the CNT end caps, generating carboxylic groups suitable for enhancing the solubility of the CNTs with improved biocompatibility [85]. It has been shown that

a highly negative charge developed Inhibitors,research,lifescience,medical as a result of the carboxylation increases the hydrophilicity of CNTs. Covalent linkage of polyethylene glycols increases the hydrophilicity and the solubility of CNTs in aqueous media Inhibitors,research,lifescience,medical as well as increasing the size which reduces the rate of clearance of CNTs through the kidneys and tends to increase the circulation Anacetrapib time in the plasma. Tour et al. proposed the functionalization of CNTs in acidic media, which yields oxidized CNTs in large and industrial scale quantities [86]. Side wall functionalization of SWCNTs through C–N bond forming substitutions of fluoronanotubes was explored by Khabashesku et al. and reported that this method offers a wide range of further SWCNTs derivatizations including their covalent binding to amino acids, DNA, and polymer matrix [87]. 3.2. Noncovalent Functionalization Noncovalent functionalization involves Van der Waals interactions, π-π interactions, and hydrophobic interactions of biocompatible functional groups with the surface of the CNT.

The highest increase was detected in Zarindasht (120 74%) and the

The highest increase was detected in Zarindasht (120.74%) and the lowest was detected in areas such as Mohr and selleckchem Dasatinib Lamerd (4.24%) from the baseline in 2004. The highest average of change among the studied calcitriol?hormone health networks belonged

to Mohr and Lamerd (324.7%) and the least change was seen in Kazeroon (54.4%). The comparison of cost per each percent of index change showed that the highest amount belonged to Shiraz with 123,486,415 Rials (approximately $13,393) and the least amount belonged to Khorambid with 922,470 Rials (approximately $100) reduction in costs. Arsanjan had the highest total percentage of change among the Inhibitors,research,lifescience,medical cities and the lowest cost per each percentage of change (figure 2). Figure 2 This figure shows the comparison of the relative efficiency cost per each percent change in health indices in the health networks after performing the family physician plan. In spite of the increase in performance indices in the four studied units, in all the province`s health

networks, the costs of health care services after performing family Inhibitors,research,lifescience,medical physician plan have had a 154.67% increase on average. The comparison of cost efficiency during the two time points of the study showed that in 78% of health networks, the cost efficiency had further reduced in 2006 compared with year 2004. Discussion Several factors affect the performance of health systems such as lack Inhibitors,research,lifescience,medical of technical efficiency because of an inappropriate and ineffective management, organization, and payment system which results in Inhibitors,research,lifescience,medical low motivation, low quality of services, and limited access.16 We found that after the implementation of the family physician plan, the healthcare costs have increased by 154.67% in all health networks in Fars province. This can be resulted from the increase in direct and indirect costs in the form of rural insurance funds for each network. Considering the necessity of cost reduction in the health system, Inhibitors,research,lifescience,medical Evans and colleagues concluded that expending more costs did not necessarily lead to better health outcomes.8 Davise and co-workers also stated

that the reduction of extra costs, investment for improvement of access and equity, and focusing on PHC are among the strategies that can substantially increase the efficiency.3 In all health networks in Fars province, the number of referrals to family physicians increased to an average of 222.45%. This is mainly Dacomitinib because of increased number of physicians and improved access to physicians in rural areas. Although this can be interpreted as a beneficial point, it can also mean more unnecessary physician visits and the over-referral of patients by physicians because of the advantages of rural insurance system. According to a report by the Health Deputy of Shiraz University of Medical Sciences, 37% of patients referring to physicians for their complaints could be treated by assistant physicians with no need for the physician’s intervention.

5,178 Age and gender have a significant influence on these measur

5,178 Age and gender have a significant influence on these measures,179,180 and depressed adolescents seem to have relatively more frequent disturbances in circadian rest-activity rhythms, sleep architecture, and RRG rhythms during sleep compared with depressed children.5,180,181 Among adolescents, the RRG sleep measures were remarkably stable when examined both during the acute depressive episode and during sustained remission, suggesting that these measures are trait-like.182,183 selleck kinase inhibitor changes in sleep

architecture and sleep-related RRG rhythms also were documented in except healthy adolescents Inhibitors,research,lifescience,medical at high risk for depression, and these changes were associated with vulnerability for depression during prospective follow-up.184-186 Additionally, baseline EEG sleep patterns differed between depressed adolescents who subsequently had a recurrent unipolar course versus those who developed bipolar illness; adolescents with Inhibitors,research,lifescience,medical unipolar course had predominantly rapid eye movement (REM) sleep changes while adolescents with bipolar course had non-REM sleep changes.187 In the same study, adolescents who subsequently developed substance use disorders had relatively normal EEG sleep patterns.101 Although EEG sleep changes in pediatric depression, particularly the childhood-onset type, show discontinuities with findings in adult Inhibitors,research,lifescience,medical depression,188,189 it is important to also emphasize the variability across studies

of both children and adolescents.5,178 The observed variability in EEG sleep changes in depressed youngsters may reflect, at least in part, heterogeneity in the longitudinal clinical course of these disorders. For example, sleep Inhibitors,research,lifescience,medical data in adults suggest distinct

biological substrates in unipolar and bipolar mood disorders. REM. latency changes were observed less frequently in bipolar depression.190,191 Sleep loss can effectively trigger the onset of mania in patients Inhibitors,research,lifescience,medical with bipolar illness,192,193 but has minimal euphorigenic effect in unipolar depression. Therapeutic sleep deprivation also appears to have different clinical effects in unipolar and bipolar patients.194 As described above, a substantial minority of youngsters initially identified as having unipolar depression subsequently develop bipolar disorder, and those with early-onset illness in particular.48 Among children, studies that excluded depressed patients with family history of Dacomitinib bipolar disorder were more likely to demonstrate EEG sleep changes compared with controls.180,195 Neuroendocrine studies There has been considerable interest in the HPA system, consistent with the possibility that depression is linked to altered responses to stress, and numerous studies have documented HPA dysregulation in adult depression.196 HPA findings in depressed children and adolescents were inconsistent.5,170 In particular, depressed children did not display changes in 24-hour Cortisol patterns.

Gaia was in the center, Ouranos all around, and there was no spac

Gaia was in the center, Ouranos all around, and there was no space between them. Gaia became pregnant and the Titans, children of Ouranos, could not be born because of the lack of space. One of the Titans, Kronos, made it possible to chase away Ouranos, and this enabled space to be created. Gaia was able to give birth to the Titans. They

later procreated, and this succession of births created time, Chronos. According to Klein, a confusion we make between time and future dates Inhibitors,research,lifescience,medical back to that myth. A major contribution from this author is the notion that time has never been thought of as what produces duration.24 Time and biology Biological clocks such as the suprachiasmatic nucleus deal with the generation of circadian rhythms.25 Many other temporal physiological functions are distributed in other brain areas, independent of the suprachiasmatic nucleus. They are the temporal coordination of spatially distributed neuronal networks, as well as brain structures that relate Inhibitors,research,lifescience,medical to Tempus, ie, the prediction and evaluation of durations. Many observations and experiments have confirmed that living species are able to measure durations. The measurement of short durations, of less than a second, are probably less dependent on attention or emotion, although these can modulate even the measurement

of short durations. The evaluation of longer durations, from seconds to hours or weeks, involves cognitive functions such as attention, Inhibitors,research,lifescience,medical emotion, and memory. More than 100 years ago, the Swiss psychiatrist Auguste Forel (1848-1931), known for his work in psychiatry, neurohistology and for his extensive studies on ants, noticed that bees came to his breakfast table regularly at the same time, even when no breakfast was being served.26 He coined the term Zeitgedächniss, or new post memory Inhibitors,research,lifescience,medical of time. Indeed, bees can be conditioned to go at a given moment of the day to a given location where food was previously provided. A theoretical model on how biological systems could measure duration, ie, how a brain system

might generate a continuous metric, Inhibitors,research,lifescience,medical was proposed by Treisman in 1963.27,28 The model proposed by Treisman provides the organism with a centralized system of time measurement. This has been criticized on the following basis: it could be that each biological function has an inbuilt duration measuring system, for example, a different one for motor action, for vision or for audition. Moreover, there might even be independent duration AV-951 measuring systems for subfunctions in each motor or perceptive system. David M. Eagleman summarized issues raised by the handling of time by the brain: A challenge for the brain is that afferent signals from the different, sensory modalities are processed at different, speeds. When receiving signals from several modalities, how does the brain determine the timing correspondence? The answer seems to be that the brain dynamically recalibrates its expectations.

Further support for this conclusion comes from an examination of

Further support for this conclusion comes from an examination of areas in the brain, where activity was modulated by symptom severity. The visual areas identified in between-group analyses as showing stronger activity in the ASD children were the only areas in the brain where activity correlated with symptom severity: the more severe the ASD symptoms, the greater the activity in these visual areas. We therefore conclude that the abnormal activity observed in children with ASD in these regions is most likely indicative of a deficit in multisensory integration, observed most substantially (at both the neural and behavioral level) in children with the greatest symptom

severity. The findings Inhibitors,research,lifescience,medical of Mongillo et al. (2008) lend further support to this interpretation as they found that SRS scores were negatively correlated with scores on the McGurk test – a test of auditory and visual speech integration (McGurk and MacDonald 1976).

Thus, consistent with our results, greater symptom selleck screening library severity is associated Inhibitors,research,lifescience,medical with less evidence of multisensory integration. The current findings – especially with regard to the positive correlation observed between symptom severity and neural activity in visual areas – are consistent with growing evidence of abnormal cortical connectivity in children with ASD (e.g., Inhibitors,research,lifescience,medical Kleinhans et al. 2008). It has been theorized that individuals with ASDs exhibit increased local connectivity, to the detriment of long-range connectivity (for review, see Minshew Inhibitors,research,lifescience,medical and Williams 2007). For example, several studies have identified thereby decreased connectivity between visual and frontal cortices (Villalobos et al. 2005; Koshino et al. 2008), and other studies have found increases in thalamocortical connectivity,

hypothesized to compensate for reduced cortico-cortical connectivity (Mizuno et al. 2006). Also, highly relevant to the current findings are studies reporting abnormal low-level visual processing (Bertone et al. 2005), visual hypersensitivity (Ashwin et al. 2009), and/or low-level Inhibitors,research,lifescience,medical visual problems (Vandenbroucke et al. 2008) in individuals with ASD. In this Carfilzomib study, audiovisual integration – which depends on the synthesis of information from primary visual and auditory cortices – may be disrupted as a result of abnormal cortico-cortical connectivity and/or a specific deficit in visual processing. Future studies are needed to address these competing accounts. Finally, our findings are in line with considerable evidence suggesting specific deficits in integrating communicative cues in individuals with ASD (Williams et al. 2004; Mongillo et al. 2008; Whitehouse and Bishop 2008; Klin et al. 2009). Recently, Mongillo et al. (2008) found that for a group of children with ASD, deficits in audiovisual integration were more salient when stimuli involved audiovisual elements of human communication (i.e.

The contaminated volumes were detected by the criteria FD > 0 5 m

The contaminated volumes were detected by the criteria FD > 0.5 mm or RMSD > 0.3%. Identified contaminated volumes were replaced with new volumes generated by linear interpolation of adjacent volumes. Volume replacement was done before band-pass filtering (Carp 2013). Figure 3 Flowchart of the fMRI data analysis in subject’s native space. The thick triple line shows the flow of the fMRI data. The motion-corrected signals were passed through a #Dasatinib Src inhibitor keyword# band-pass technical support filter with the cut-off

frequencies of 0.01 and 0.08 Hz. This band-pass filter has three functions: First, it is an antialiasing filter to remove aliasing due to 0.5 Hz sampling of the BOLD signal; second, it eliminates the higher frequency (>0.1 Hz) fluctuations of the BOLD signal that are mainly a reflection of respiration signal modulated by heartbeat signal; third, it removes the high-power low-frequency noise (the Inhibitors,research,lifescience,medical power spectrum of the noise is related to the frequency by 1/f factor). We used flsmaths–bptf to do the filtering in this study (Jenkinson et al. 2012). After filtering, the first few volumes were discarded due to the lag of the digital filter. Anecdotal observations in our division showed that digital filter lags (almost the same as the order of the filter) often induce minor correlations Inhibitors,research,lifescience,medical between the signals. Finally, we residualized

the motion-corrected, scrubbed, and temporally filtered volumes by regressing out the FD, RMSD, left and right hemisphere white matter, and lateral ventricular signals (Birn et al. 2006). We expected that volume scrubbing would effectively remove Inhibitors,research,lifescience,medical sudden but large movements of the head and that subsequent residualization would further remove the effect of steady but small motion of the head often found in older subjects due to respiration or tremor. FMRI analysis Inhibitors,research,lifescience,medical in native space Figure 3

presents the flowchart of the processes in our native space method. T1 image segmentation and parcellation were done by FreeSurfer. The FreeSurfer segmentation and parcellation results were then transferred to the subject’s native space. A separate mask was generated for every segmented subcortical and parcellated cortical region for each subject. Intermodal, intrasubject, rigid-body registration of Drug_discovery fMRI reference image and T1 scan is a challenging task. We examined three intermodal registration methods, FMRIB’s linear image registration tool (FLIRT) (Jenkinson et al. 2012), boundary-based registration (BBR) (Greve and Fischl 2009), and advanced normalization tools (ANTS) (Avants et al. 2011), for 10 randomly selected subjects in our data set. Visual inspection showed that the results of FLIRT and BBR algorithms are very similar and outperform ANTS. Even though BBR algorithm claims to be robust to B0 field inhomogeneity (Greve and Fischl 2009), FLIRT performance was slightly better than BBR in registering the two modalities.

B cells showed no changes These early results were theorized to

B cells showed no changes. These early results were theorized to occur because of the general stress response to such a distressing life event (as opposed to a grief-specific response). Research on multiple aspects of immune functioning during bereavement continued through the 1980s,25,26 the 1990s)27-31 and the 2000s.9,32,33 Generally, decreased natural killer cell cytotoxicity and poorer lymphocytic response to pathogens was found for bereaved individuals compared with nonbereaved individuals, and found particularly in early Inhibitors,research,lifescience,medical bereavement as compared with later bereavement.

Of course, negative findings are less likely to be published, but overall, these findings are quite consistent. In addition, particular subpopulations have been studied because of their compromised immune status. A number of studies have investigated HIV-positive individuals,

and their experience of the death of a partner.28,29,34 In Inhibitors,research,lifescience,medical addition, bereaved older adults have been investigated, and they follow a similar pattern with the additional finding of reduced antibody titers to vaccination.32 However, bereaved Inhibitors,research,lifescience,medical older adults have not demonstrated greater proinflammatory cytokines.35 Through this expansion of immunological research, the theoretical perspective primarily posited that bereavement was an example of a nonspecific stressor (compared with other stressors such as space shuttle touchdown, significant illness of a spouse, insomnia, and other stressors summed from life event checklists). Additional moderators and mediators have been considered in different

studies (eg, depressive disorder, active coping, finding meaning in the loss). All of these studies hypothesize that bereavement is a form of life stress, which although very severe, operates through known stress-response systems. To state this Inhibitors,research,lifescience,medical differently, the investigators presume that the distress leads to increases in the figlit-or-flight response, and this leads to reduced cellular immune functioning. Regarding this general stress theory, some studies that investigated Cortisol and immune parameters simultaneously and have not found changes in Cortisol that could be linked Inhibitors,research,lifescience,medical to the immune decrements,24,30,36 while others have found an association.9,28,33 One theory is that bereavement AV-951 stress leads to depression, and only depressed bereaved persons show immune decrements. especially Several studies26,31 found no immune functioning or immune population differences between bereaved and nonbereaved, but did find that widows who were depressed had lower natural killer cell activity and lower responsivity to mitogen stimulation than widows who were not depressed. Nonetheless, none of the authors suggest that there is an immune response that is specific to bereavement stress, but rather that bereavement is one example of the general stress response. None of these studies have used a diagnosis of CG to shed light on who has immune impairment and UFA dysregulation in response to a death event.

In particular, noninvasive brain stimulation offers a convenient

In particular, noninvasive brain stimulation offers a convenient tool to directly target the network level by altering the temporal structure of neuronal activity. With the exception of a few novel and rather poorly understood brain stimulation approaches such as ultrasound4,5 and laser,6 the vast majority of noninvasive brain stimulation is based on the activator Calcitriol application of electric and magnetic fields to modulate neuronal activity. Yet, since the development of the Inhibitors,research,lifescience,medical electroencephalogram (EEG) early in the 20th century,7 we know that network activity in brains also generates its own, endogenous, electric fields.8 In this review,

we will discuss both endogenous and exogenous electric fields and will highlight the promising opportunities for the rational design of noninvasive brain stimulation approaches for the treatment Inhibitors,research,lifescience,medical of psychiatric disorders. In particular, there will be a focus on the modulation of cortical oscillations, a hallmark of physiological and pathological

brain function.9,10 Ubiquitous neuronal network signal as a convenient epiphenomenon? Neuronal signaling relies on the generation and transmission of transient electric impulses that represent the fundamental information unit in the brain.11,12 The canonical model of neural information processing is based on the notion that changes of the electric potential inside neurons relative Inhibitors,research,lifescience,medical to the constant electric potential Inhibitors,research,lifescience,medical outside of the neuron determines the membrane voltage, and therefore the functional state of individual neurons.13 Yet, the vast majority of selleck kinase inhibitor neurophysiology studies are based on measurements of changes in the extracellular voltage such as the classical EEG, broadly used in both clinical and basic science settings, and the local field potential (LFP), an invasive recording of the extracellular voltage routinely performed in neuroscience animal studies.14 These fluctuations of extracellular voltage represent the endogenous electric field and reflect the activity of a large number of (synchronized) neurons; they have provided the basis for numerous discoveries Inhibitors,research,lifescience,medical AV-951 about physiological

and pathological states in the brain. These electric signals have routinely been considered an epiphenomenon in neuroscience, in the sense that the endogenous electric field plays no functional (”active“) role per se, but rather, represents a convenient side product of neuronal network activity to the benefit of the researcher or clinician who wants to measure brain activity. This view was supported by the realization that endogenous electric fields were comparably low in magnitude (around 1 V/m) and therefore unlikely to be powerful enough to directly modulate neuronal signaling. Studies which demonstrated that such weak electric fields change the membrane voltage only by an amount much smaller (typically about 0.