Cellular distribution of the receptors differs with the type I receptor generally expressed Y-27632 concentration by hematopoietic cells and type II by non-hematopoietic cells due to differing expression of the γc and IL-13Rα1 subunits, while macrophages express both type I and II receptors. Engagement of IL-4/IL-13 to the receptors triggers cell signalling via JAK/STAT6 dependent mechanisms [25]. A second receptor, IL-13Rα2, binds IL-13 with high affinity and is thought to be a decoy receptor sequestering IL-13 [24], although some studies suggest an uncharacterised signalling activity [26]. Previously, Ahlers et al. [27] demonstrated that soluble IL-13Rα2-Fc decoy

receptor together with GM-CSF and CD40L as molecular adjuvants can enhance magnitude HIV Env-specific CD8+ CTL peptide vaccine response. However, IL-13Rα2-Fc protein used alone without other co-stimulators failed MEK inhibitor to enhance CTL magnitude or activity. Consistent with this finding we have also found that, a single administration of soluble IL-13Rα2-Fc protein together with FPV-HIV made no difference

in HIV-specific CD8+ T cell numbers or T cell avidity [23]. In contrast, HIV vaccines co-expressing IL-13Rα2 decoy receptor was able to sequester free IL-13 and greatly enhance magnitude, functional avidity and poly-functionality of the HIV Gag-specific CD8+ T cell response [23]. A number of IL-4 derivatives that either mutate or delete the essential tyrosine residue found in the C-terminal region of both human and mouse cytokines have been developed which bind to cellular IL-4Rα with high

affinity without stimulating cell signalling and block activation 5-Fluoracil by both endogenous IL-4 and IL-13 [28], [29], [30] and [31]. To avoid introducing novel viral expressed “IL-4 antigens” due to amino acid substitutions we have constructed recombinant FPV and VV co-expressing a soluble mouse IL-4 protein containing a short C-terminal deletion encompassing the essential Y119, IL-4C118, while retaining high affinity binding to both IL-4R types I and II and blocking IL-4/IL-13 cell signalling (see Suppl. Diagram 1). In this study we have evaluated the efficacy of this novel IL-4R antagonist HIV vaccine, specifically the ability to not only induce high avidity CD8+ T cells but also B cell immunity. In this study the HIV-specific T cell responses were evaluated against the BALB/c Gag197–205 AMQMLKETI immune-dominant CD8 T cell epitope [32]. As we have previously shown that CD8+ T cells specific for the immuno-dominant epitope represent approximately 80% of the total Gag response in an FPV-HIV/VV-HIV immunisation setting [33]. The B cell responses were measured against the total HIV P55 Gag protein. The mouse IL-4C118 cDNA was isolated using the reverse transcriptase polymerase chain reaction (RT-PCR) method and the Qiagen RT-PCR kit to amplify the cDNA from mouse spleen total RNA.

B.N., J.A.C., A.M., R.J.). This trial was registered at clinicaltrials.gov under number: NCT01487629. The authors would like to thank Prof Dr Klaus

Dietz, professor emeritus of Medical Biometry (University of Tübingen–Germany), for review of and constructive comments on the statistical analysis. “
“Mayer WJ, Mayer WJ, Klaproth OK, Hengerer FH, Kohnen T. Impact of Crystalline Lens Opacification on Effective Phacoemulsification Time in Femtosecond Laser-Assisted Cataract Surgery. Am J Ophthalmol 2014;157(2):426–432. In the February Y-27632 datasheet 2014 issue, an error occurred in the first sentence of the “Methods” section: “One hundred fifty eyes of 68 patients with senile cataract were enrolled in this retrospective, nonrandomized cases series between September 2012 and May 2013,” 68 patients should have been revised to 86 patients. The correct number is also written in the abstract. The authors regret this error. “
“Charbel Issa P, Finger RP, Kruse K, Baumüller S, Scholl HPN, and Holz FG. Monthly Ranibizumab for Nonproliferative Macular Telangiectasia Type 2: A 12-Month Prospective Study. Am J Ophthalmol 2011; selleck chemicals llc 151(5): 876-886. In the May 2011 issue of the American Journal of Ophthalmology,

an error is reported in the above article. Towards the end of the last paragraph of the article, the text reads, “While the unchanged distance visual acuity at the 12 month follow-up would have suggested a stable disease course, microperimetry revealed a progressive paracentral loss of retinal light sensitivity (study eye: −2.3dB; SD 2.4; p= 4-Aminobutyrate aminotransferase 0.01; fellow eye: 1.3dB; SD 1.6; p = 0.03; assessed were 9 testing points covering an area of 3×3 degrees temporal to the

foveal center) due to continuing photoreceptor degeneration.”30 The value for “fellow eye” in the above paragraph incorrectly appears as “1.3dB.” The correct value is “−1.3db. The authors regret this error. “
“The 3rd World Congress on Controversies in Ophthalmology (COPHy), March 22–25, 2012, Istanbul. Website: http://www.comtecmed.com/COPHy/2012/ COPHy Istanbul will be devoted to evidence-based debates and discussions amongst chairpersons, speakers and the audience, all of whom will examine and analyze the most relevant issues raised during the course of 2011 within the field of Ophthalmology. Simultaneous sessions will emphasize controversies within anterior segment, retina, and glaucoma. “
“Figure options Download full-size image Download high-quality image (251 K) Download as PowerPoint slide Dr Alberto Urrets-Zavalía Jr, who passed away on July 31, 2010, at the age of 89, was one of the most influential Argentine ophthalmologists of the 20th century. Born in Córdoba (Argentina) on September 30, 1920, he was the son of a nationally renowned ophthalmologist and the eldest of 6 children. In 1953, he founded in Córdoba the Cornea and Glaucoma Surgical Center.

Under current technological limitations, the US Department of Agriculture (USDA) in collaboration with the University of

California at Berkeley are trying to develop a genetically engineered switchgrass variety that contains up to 250% more starch than conventional varieties [12] and [13]. This would allow for increasing the economic efficiency of sugar yields and minimizing the final switchgrass-based biofuels costs. If combined with the enzymatic modifications as described above, the production costs of cellulosic ethanol could be reduced substantially. Linsitinib Another feedstock to be potentially used for cellulosic ethanol production in the future is elephant grass (napiergrass) (Pennisetum purpureum) that was introduced to the US from Africa in 1913. This tropical plant is fairly drought-tolerant, grows well on marginal lands and filters nutrients out of runoff in riparian areas. In addition, it does not require irrigation and is capable of producing biomass until the first frost. The main technological requirement and challenge to make napiergrass an efficient and competitive feedstock is to

improve its yields and increase disease resistance [14] and [15]. Poplar has been considered for a long time as a viable Alpelisib in vivo and prospective feedstock for cellulosic ethanol production in the US. Poplar is drought-tolerant and capable of growing on marginal lands. If indeed grown on abundant or marginal land, it does not compete with other crops for food and animal feed. If cultivated on a biofuel farm, poplar trees create favorable wildlife habitats and provide recreational services. By removing

contaminants from soil, poplar has a valuable potential of soil remediation (phytoremediation) [16], which clearly benefits other parts of the ecosystem chain. Growing poplar trees is said to be more fuel efficient and generates a lower carbon footprint Rebamipide than other annual food crops. Its growth rate is considerably slower than that of biofuels oil crops (e.g., crambe and camelina) [17]. However, this problem could be mitigated by applying biochemical modifications, as discussed in the previous section, or nocturnal photosynthesis that allows poplar to absorb carbon dioxide also at night. This feature allows the plants to reach a higher growth rate with lower water requirements (8–16 inches = 203–406 mm) of precipitation annually) as compared with traditional biofuel crops that require 20–40 inches/year (508–1,016 mm/year) [17]. Another possibility to increase poplar growth rates, which also constitutes a major challenge nowadays, is growing genetically modified poplar species that would hold the nocturnal photosynthesis mechanism and thus constitute a feedstock even more tolerant to drought than the conventional poplar species [18]. One of the possible limitations could be harvesting, transport and storage costs. Another feedstock theoretically considered for ethanol production is orange (citrus fruit) peels. Global agriculture produces about 15.

In this review we highlight progress since 2010 in determining genetic susceptibility to prion diseases. The use of human genome-wide association studies (GWAS) and complementary mouse studies reinforce

the key role of PRNP and identify new genetic modifiers. We outline the challenge of verifying the role of putative modifiers and propose a way find protocol forward for gene identification and validation ( Figure 1). Recent work has focussed on the collection of large patient cohorts for GWAS, which has necessarily been an international collaborative endeavour given that human prion diseases are rare. As a generality from common diseases, genetic risk factors discovered by GWAS have been modest in their effects (odds ratios 1–1.2) requiring sample sizes of several thousand to have the statistical power required for unequivocal detection of significant variants. Two collaborative groups are working in prion disease GWAS. The UK MRC Prion Unit in collaboration with the Universities of Munich, Gottingen and Perth has conducted a GWAS of sporadic CJD, variant CJD, iatrogenic CJD, inherited prion disease, and kuru involving over 2000 samples [7 and 8••]. A Europe-wide collaboration

led by Dutch and Spanish investigators published a GWAS of vCJD involving 93 samples [9••]. In these studies, the PRNP locus was unequivocally and strongly associated with risk of prion disease, driven by the known Pembrolizumab in vitro coding variation at PRNP codon 129. In the European vCJD GWAS two single nucleotide polymorphisms (SNPs) (rs4921542 and rs7565981) reached genome-wide significance after pooling discovery and replication populations. Rs4921542 (p = 1.6 × 10−8) is an intronic variant in the myotubularin related protein 7 gene (MTMR7), which is specifically expressed in the central nervous system and dephosphorylates phosphatidylinositol 3-phosphate and inositol 1,3-bisphosphate. Rs7565981 (p = 4.2 × 10−8) is in an intergenic region upstream of the neuronal PAS (per-ARNT-sim) domain-containing protein 2 gene (NPAS2), a regulatory gene belonging to a family of transcription factors. In the UK-German sporadic CJD study, no non-PRNP loci achieved genome-wide signficance. SNPs at the ZBTB38-RASA2

locus were associated with CJD in the UK (rs295301, p = 3.13 × 10−8) but these SNPs showed no replication evidence of association in German sporadic CJD or in kuru based tests. Overall, it is likely that the PRNP locus Branched chain aminotransferase contains the only strong risk factors which act universally across human prion diseases. Whilst some genome wide significant loci have been proposed in vCJD, the low incidence of this condition means that there is no way at present to generate unequivocal genetic evidence at these loci. The collective data are most consistent with the findings in other diseases, of strong effects being the exception but many risk loci of modest effects. In prion disease this will require large collaborative GWAS in sCJD to provide definitive statistical evidence of these weak effects.

2. To determine the overlap of these TCDD-responsive genes across the different strains/lines, we analyzed the number of responsive genes across strains. We merged the data from LBH589 research buy RAT230-2 and RAE230-A microarrays by keeping genes common to both and visualized those that were TCDD-responsive (Fig. 3B). There is a log-decrease in the number of responsive genes as the number of strains increases, indicating very large inter-strain differences in the number of TCDD-responsive genes.

We found a set of 11 genes that responded significantly to TCDD in all six strains/lines (Fig. 3C). Outside of this core, strains differ significantly in their responses to TCDD and there is minimal overlap between them (Fig. 3D). Interestingly, F344 rats showed greater similarity to L-E rats (25.3% overlap) than to H/W rats (9.8% overlap); Wis rats had similar numbers of gene alterations as H/W rats but greater similarity in specific genes to L-E (41.8% overlap) than to H/W rats (22.4% overlap). We previously contrasted the transcriptomic responses to TCDD between L-E and H/W rats at 4 and 10 days following

TCDD treatment at 100 μg/kg and found considerable overlap between the two strains at both time points (Boutros et al., 2011). Similarly, we looked for overlap between different rat strains at an early time point (19 h) to identify genes that may have critical roles in triggering TCDD toxicity. Consistent with our previous data, the 11 genes PF-02341066 price that exhibited the greatest magnitude of response and were most consistent across all 6 strains/lines at the onset of TCDD toxicity are classic AHR-regulated genes, such as Cyp1a1, Cyp1b1, Nqo1, and Tiparp. All 11 of these genes exhibited consistent Edoxaban directions and magnitudes of change across all six strains and lines ( Fig. 4A). We hypothesized that genes showing differential gene expression between sensitive and resistant rat strains are strong candidates to mediate susceptibility to dioxin lethality. To test this hypothesis, we focused on genes that showed divergent responses between rat strains with differing TCDD-sensitivity.

We identified genes that were altered specifically in highly or moderately TCDD-sensitive L-E, F344, and Wis rats but not in resistant H/W rats (Fig. 4B). Here we see that although multiple genes showed the same directionality of change across all 6 strains, there are differences in the magnitude of response across the different strains, with some genes having a 4-fold difference in gene expression between strains. To examine whether genes identified from the above analysis belong to a specific pathway, perhaps leading to conserved strain-independent TCDD toxicity, we employed functional analysis for the 100 genes that showed the smallest adjusted p-values for each strain. We examined GO terms that have FDR of less than or equal to 0.

3 months in group 2 and 8.6 months in group 1 (Tables 3 and 4). Twenty-six percent of participants in our high-risk clinical CT lung screening program did not meet group 1 inclusion criteria and qualified for screening through group 2 (Table 1, Fig. 2). Applied nationwide, a group 2 rate of 26% would equate to approximately 2 million Americans at high risk for lung cancer outside the entry criteria of the NLST

[6]. Additionally, as nearly one-third of our group 2 population failed to meet group 1 criteria solely because they quit smoking >15 years previously, 600,000 former smokers between 55 and 74 of age with >30-pack-year smoking histories could lose access to screening Cyclopamine datasheet with national eligibility limited to group 1. Enrolling group 2 individuals does require additional provider and insurer infrastructure to assess risk factors beyond age and smoking history. To efficiently manage intake resources required in our clinical CT lung screening program, once a candidate was found to have a qualifying

risk factor for group 2, the presence of additional risk factors was not formally assessed. As such, it is possible that the order in which risk factors were assessed during the enrollment process may have influenced the breakdown of qualifying risk factors in our group 2 population. Future research is needed to comprehensively address the presence MK2206 of additional risk factors in this group. To be considered for screening, patients were required to be asymptomatic and were instructed in writing and verbally at multiple points to forgo screening for 12 weeks after clinical symptoms of pulmonary

infection had resolved. Despite these focused efforts, 6.5% of patients had radiographic evidence of evolving or resolving infection on their screening examinations, with similar frequencies in groups 1 and 2. Our rate of clinically significant incidental findings was also nearly identical for group 1 and group 2 at approximately 6.0% and was significantly less than the 10.2% reported on the prevalence screen in the NLST [6]. This difference may be explained by the fact that approximately 20% of our screened patients had prior cross-sectional imaging of at least part of the chest available for review at time of examination interpretation or that some cases of suspected infection were included in this category OSBPL9 in the NLST. The overall average age and smoking history of group 2 in our study cohort were slightly lower than those of group 1, with a more notable difference in duration of smoking cessation among former smokers in each group (18.5 years in group 2 vs 6.7 years in group 1) (Table 1). Despite these statistically significant differences in age, smoking history, and smoking cessation characteristics, there was no statistically significant difference in the rate of positive results between group 2 and group 1, and the positive rates are similar to those reported on the prevalence screen in the NLST [11].

All participants reported to be native English http://www.selleckchem.com/products/VX-765.html speaking, right-handed, which was confirmed by the Edinburgh Inventory ( Oldfield, 1971), and had no hearing deficits. Additional item measures were taken to screen for and exclude any individuals

that were currently suffering from, or reported any previous history of neurological conditions, psychiatric illnesses or impaired language ability. The sample was divided into high (n = 64) and low (n = 68) schizotypal personality groups by the median of the total Schizotypal Personality Questionnaire (SPQ) score (median = 17; range, 1–46; see Table 1). This approach allowed for the assessment of range-bound schizotypy effects and has previously been used elsewhere (e.g., Hori, Ozeki, Terada, & Kunugi, 2008; Langdon & Coltheart, 2004). No significant differences in demographic variables

were found between the two groups, indicating Ku-0059436 manufacturer equal dispersions of sex [X2 (1, N = 132) = 067, p > .05] and age [t(119) = 1.48, p > .05]. In addition, all participants were treated in accordance with the Declaration of Helsinki ( International Committee of Medical Journal Editors, 1991). The auditory stimuli used within the present dichotic listening task consisted of four words (‘dower’, ‘tower’, ‘power’, and ‘bower’), each pronounced in four different emotional tones (happy, sad, angry, and neutral), resulting in 16 separate word–emotion combinations. These were spoken by an adult male and recorded using a digital recorder. After the stimuli were obtained, they were edited to a common length of 560 ms and equalised in loudness. Originally four versions of each word–emotion combination were gathered,

totalling 64 recordings. After editing, these stimuli were presented to a group of 4 participants who were asked to report the word and emotional tone and to rate the intensity (on a scale of 1–5) with which it was spoken. From this, the final stimuli were constructed by selecting the 16 word–emotion sound files that were IKBKE most correctly identified. To ensure that these 16 recordings were perceived accurately, an additional ten participants were asked to report each word and emotional tone. The emotions were recognised with a minimum accuracy of 69% (M = 81.4) and words were identified with a minimum accuracy of 94% (M = 98.8). Following confirmation of the stimuli, all potential pairings of word–emotion combinations were created, generating 144 stimulus pairs in total. These stimuli were presented over headphones and the experiment was run on SuperLab software. This 10-item scale requires participants to specify their hand preference for 10 activities including writing, drawing, throwing, and striking a match. Participants are requested to indicate whether they predominantly use their right hand, left hand, or have no preference. These answers are scored +10, −10, and 0, respectively.

Quilizumab is an afucosylated monoclonal antibody against the M1 prime domain of human membrane IgE [29], which enables the direct therapeutic targeting of IgE-switched cells. The effect of quilizumab on IgE production has been assessed in three independent small phase I and II studies [54••]. In patients

with mild asthma, quilizumab treatment completely inhibited new allergen-specific IgE production induced by whole lung allergen challenge [54••]. In addition, quilizumab treatment resulted in a gradual reduction in total serum IgE levels in healthy volunteers, patients with allergic rhinitis, and patients with mild asthma [54••]. The kinetics and extent of serum IgE reduction were MDV3100 research buy similar following one or several dose administrations of quilizumab and were also similar to the reductions in total serum IgE observed upon blockade of IL-13 or IL-4Rα, consistent with this proportion of total serum IgE arising from short-lived plasma cells generated from ongoing IgE B cell responses. The residual total serum IgE levels that were not affected by quilizumab treatment may have been produced by long-lived IgE plasma cells that were not targeted

by quilizumab. Interestingly, the reductions in total serum IgE were sustained at least six months after the last dose of quilizumab, suggesting that treatment with quilizumab may have abrogated some memory IgE responses that were contributing Vincristine concentration to ongoing IgE production, which were not regenerated upon the cessation of quilizumab therapy. Studies of IgE production using genetically modified IgE reporter mice have revealed that most IgE in mice is produced by short-lived IgE plasma cells arising from ongoing IgE B cell responses. IgE responses in mice are transient, due to a limited persistence of IgE germinal center responses and the short life span of most IgE-producing plasma cells. IgE memory responses remain poorly understood, and the sources of IgE memory are controversial, although both IgE and IgG1 memory B cells have been implicated. Further studies of IgE

production in mice are needed to better define 3-mercaptopyruvate sulfurtransferase the mechanisms that limit IgE germinal center responses and predispose IgE-switched cells to differentiate into short-lived plasma cells, as well as the sources of IgE memory. Results of clinical studies of agents targeting IL-4 and/or IL-13, as well as membrane IgE, indicate that a significant proportion of IgE in humans arises from short-lived IgE plasma cells and ongoing IgE B cell responses, similar to that observed in mice. However, the human clinical studies also suggest that a major proportion of IgE in humans, larger than that observed in mice, may arise from long-lived IgE plasma cells. It should be noted that differences in mouse models of IgE production compared to IgE production in humans may account for the differences in the effects of therapeutics in mice versus humans.

An adequate mucosal bleb could not be created along the greater curvature of the stomach, as mentioned previously, and thus ES was not attempted at this location. Precutting by using the needle-knife was successfully and safely performed along the anterior wall in 3 of 3 attempts. There were no procedure-related bleeding and no perforations. Gross examination of the stomach

showed that the histological changes did not extend to the muscularis propria with no evidence of perforation. Simulated papillae were successfully created by using MucoUp in 13 (82%) areas of the porcine stomach except at the greater curvature (Table 2). An experienced endoscopist performed ES in all simulated papillae by using the pull-type sphincterotome (Fig. www.selleckchem.com/products/MS-275.html 6; Video 3, available

online at www.giejournal.org). Trainee 1 could also perform ES at all locations except the lesser curvature. On the other hand, trainee 2 was only able to perform ES once at the anterior gastric wall. Simulated papillae were successfully created by using MucoUp in all 16 areas of the porcine rectum (Table 3). An experienced endoscopist and 2 trainees were able to successfully perform ES (Fig. 7; Video 4, available Dabrafenib manufacturer online at www.giejournal.org) and EP (Fig. 8A and B; Video 5; available online at www.giejournal.org) in all simulated papillae. ES is the most commonly performed procedure Progesterone during ERCP and one of the most dangerous because of the risks of pancreatitis,

hemorrhage, and perforation. Newly developed high-frequency current generators equipped with automatic control systems have been shown to be safe for ES15 and 16 to prevent a “zipper cut.”17 However, manipulation of the sphincterotome to direct the incision toward the 12-o’clock position by torquing the duodenoscope, up-angulation, movement of the elevator, and adjustment of the sphincterotome, barring all current challenges that must be mastered to optimize the sphincterotomy and avoid adverse events. Recently, in vivo and ex vivo ERCP simulation animal models4, 5, 6, 8, 10 and 11 were created to provide more realistic training models compared with computer-based simulators. Furthermore, animal models allow training that does not endanger patients and are relatively inexpensive. However, there are no ideal simulation devices or animal models for ES training because the models need to allow repeated ES procedures. To overcome this issue, Matthes and Cohen10 created a “neo-papilla” by using a chicken heart that can be exchanged as often as needed and available for ES training courses in the United States.

–MA. Tiller mortality began at PI, reached a peak in the PI–BT stage, and then gradually decreased with time until maturity. At the Max.–PI stage, DS rice showed higher tiller mortality than TP rice but

lower at BT–HD and HD–12DAH under either CT or NT. At PI–BT, higher tiller mortality was observed for CTTP (29.1%) and CTDS (29.4%) and NTDS showed lower tiller mortality than NTTP but with no significant difference. At the Max.–MA stage, the difference in tiller mortality between DS and TP was the smallest (Fig. 3). Both tillering duration (TD) and tillering rate (TR) varied significantly among the treatments. The TD was longer under TP than DS but TR was higher under DS than TP in either CT or NT. TD was longer in CTTP (59 days) followed by NTTP and lower duration was observed for

NTDS Epacadostat concentration and CTDS methods. NTDS had higher TR (15.3 m− 2 day− 1) followed by CTDS. There was no significant difference in TR between CTTP and NTTP (8.8 and 8.0 m− 2 day− 1) respectively (Fig. 4). There was a significant correlation between panicle number per m2 MK0683 clinical trial and maximum tiller number per m2, but not between maximum tiller number and panicle-bearing tiller rate (Fig. 5). The dry weight of the vegetative part of tillers varied significantly among the treatments at all crop growth stages. The tiller dry weight gradually increased until HD and decreased at the MA stage. TP under either CT or NT had higher tiller dry weight than DS except at the tillering stage. NTTP had higher tiller dry weight than CTTP at all growth stages eltoprazine except the tillering and MA stages. However, CTDS produced higher tiller dry weight than NTDS at all growth stages except the tillering and HD stages. Tiller dry weight was higher at the HD stage in all treatments and NTTP had

higher (4.3 g) tiller dry weight which was statistically not different from that of CTTP. Also there was no significant difference in tiller dry weight between NTDS and CTDS at the HD stage (Fig. 6). Leaf area (cm2 tiller− 1) varied significantly among the treatments at all growth stages of the crop. There were significant differences among establishment methods on all sampling dates. Leaf area increased sharply from the Max. to the BT stage, then slightly increased at the HD stage, and then gradually decreased with time. Leaf area per tiller was always higher under TP than DS at all growth stages. CTTP always had higher leaf area than NTTP, and CTDS than NTDS (Fig. 7). Number of spikelet per cm of panicle varied significantly among the treatments. CTTP and NTTP had significantly higher numbers of spikelet per cm of panicle than CTDS and NTDS. Panicle dry weight at maturity varied significantly among the treatments. Panicle dry weight under TP was higher than that under DS under either CT or NT. CTTP had heavier panicles (4.3 g) than NTTP. NTDS and CTDS were similar in panicle dry weight. The TP method resulted in 12% longer and heavier panicles than DS.