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Emmprin, a glycoprotein containing two Ig domains, is enriched on tumor cell surfaces and stimulates matrix metalloproteinase (MMP) production by adjacent stromal cells. Its first Ig domain (ECI) contains the biologically active site. The dependence of emmprin activity on N-glycosylation is controversial. We investigated whether synthetic ECI with the shortest sugar is functionally active.
The whole ECI peptides carrying sugar chains, a chitobiose unit or N-linked core pentasaccharide, were synthesized by the thioester method and added to fibroblasts to examine whether they stimulate MMP-2 production.
ECI carrying a chitobiose unit, ECI-(GlcNAc) 2, but not ECI without a chitobiose unit or the chitobiose unit alone, dose-dependently stimulated MMP-2 production by fibroblasts. ECI with longer chitobiose units, ECI-[(Man)3(GlcNAc)2], also stimulated MMP-2 production, but the extent of its stimulation was lower than that of ECI-(GlcNAc)2.
Our results indicate that ECI can mimic emmprin activity when substituted with chitobiose, the disaccharide with which N-glycosylation starts.
Matrix metalloproteinases (MMPs) play an essential role in remodeling of extracellular matrices (ECMs) involved in various biological processes, such as inflammation, tissue regeneration and tumor invasion. Among the MMPs, gelatinase A (MMP-2) is the most abundant MMP and frequently correlates with malignant progression and invasive behavior of tumor cells [1]. In situ hybridization studies of human surgical specimens have shown that stromal fibroblasts are the predominant source of MMP-2 in the majority of carcinomas [2-4]. Malignant cells stimulate nearby fibroblasts to produce MMPs via soluble cytokines and growth factors or through cell surface interactions mediated by plasma membrane proteins, such as emmprin [5]. Emmprin, also known as basigin/CD147, is an integral plasma membrane glycoprotein of the Ig superfamily that contains two extracellular Ig domains [6]. Expression of emmprin is upregulated in human malignant tumors, such as breast, lung and bladder carcinomas, malignant melanomas, gliomas and lymphomas, compared with their normal counterparts [7-11]. In malignant tumors, emmprin acts as a modulator of tumor-stroma cross-talk, since it mediates not only MMP production but also tumor angiogenesis through the stimulation of vascular endothelial growth factor (VEGF) expression [12], induction of activated stromal myofibroblasts [13], and anchorage-independent growth and multidrug resistance in a hyaluronan-dependent fashion [14-16]. The activity-blocking monoclonal antibody (mAb), E11F4, recognizes the first Ig domain (ECI) of emmprin, implying that this region of emmprin contains the structure responsible for the activity of this protein [5,6]. Moreover, it is reported that emmprin-induced stimulation of MMP production in fibroblasts is dependent on N-glycosylation of its extracellular domains [17,18]. However, it has been reported recently that nonglycosylated recombinant emmprin could stimulate fibroblasts to express the mRNAs of MMP-1, 2 and 3 [19]. The objective of the present study was to determine whether the activity of synthetic emmprin ECI peptides, with or without a chitobiose unit (GlcNAc-GlcNAc), the disaccharide with which N-glycosylation starts, mimics that of emmprin. The results showed that synthetic ECI substituted with a chitobiose unit, but not ECI alone, stimulates fibroblasts to produce MMP-2.
ECI (34-94th a.a.) carrying a chitobiose unit or N-linked core pentasaccharide at Asn44 was synthesized by the thioester method as described previously (Figure 1) [20-22]. ECI carrying one or two GlcNAc or N-linked core pentasaccharide [(Man)3(GlcNAc)2] was dissolved in dimethyl sulfoxide (DMSO). The final concentration of DMSO in the culture medium was less than 0.01%. At this concentration, the solvents alone showed no cytotoxic effects or any detectable effects on MMP production.
Figure 1. Molecular structure of the emmprin molecule and schema of synthetic ECI carrying a chitobiose unit or N-linked core pentasaccharide. ECI, the first extracellular Ig domain; ECII, the second extracellular Ig domain.
Cell culture
Human adult fibroblasts, MBT-3 and ST353, were obtained from a metastatic tumor in the cerebellum from a primary lung adenocarcinoma [23] and nonlesional dermis around nodular fasciitis [24], respectively. The tumor cell line FU-EPS-1 was established from a patient with epithelioid sarcoma who had not received any chemotherapy before surgical resection [25]. These cell lines were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and antibiotics (100 U/ml penicillin G and 100 μg/ml streptomycin) in a humidified atmosphere of 5% CO2 at 37°C.
Co-culture experiments
Co-culture experiments were performed as described previously [24]. Briefly, cultures containing either fibroblasts, tumor cells or both were established in 20-mm diameter wells containing 1.0 ml DMEM with 10% FBS. For co-cultures, the same number (4 × 104) of fibroblasts and tumor cells were incubated. The cells were allowed to attach for 24 h at 37°C, after which their culture media were replaced with fresh serum-free (SF) DMEM containing 0.2% lactalbumin hydrolysate (LH) (0.5 ml/well) prior to the start of the experiment. Experiments under each condition were performed in triplicate wells. The culture media were replaced with fresh SF DMEM at 3 days and harvested at 6 days. The harvested media were used for immunoblotting and enzyme immunoassay.
Treatment of fibroblasts with ECI-(GlcNAc)1 or 2, ECI-[(Man)3(GlcNAc)2], Asn44-(GlcNAc)2, or ECI alone
Fibroblasts were allowed to attach for 24 h in DMEM with 10% FBS, then their culture media were replaced with fresh SF DMEM containing 0.2% LH and ECI peptides with or without chitobiose units at various concentrations. Experiments under each condition were performed in triplicate wells. The culture media and cells were harvested at 3 days, and used for immunoblotting, enzyme immunoassay, RNA extraction and Northern blot analysis. For Northern blot analysis, cells in triplicate wells were combined to isolate poly(A)+RNA enough for the assay.
Inhibition experiments using anti-emmprin blocking antibody (UM-8D6, Ancell Corporation, Bayport, MN) were performed as described previously [23]. Briefly, ECI peptides with chitobiose units [ECI-(GlcNAc)2] were preincubated with the blocking antibody in SF DMEM containing 0.2% LH at 37°C for 45 min and then added to fibroblasts (4 × 104). Their media were replaced once with fresh SF DMEM containing [ECI-(GlcNAc)2] and the blocking antibody at 3 days, and the culture media were harvested at 6 days.
RNA isolation and Northern blot analysis
Poly(A)+RNA was isolated from cultured cells using the Fast Track mRNA isolation kit (Invitrogen, San Diego, CA). Northern blotting was performed as described previously [9]. Cloned cDNA (1,752 bp) encoding human MMP-2 was used as a probe. For internal control of loading, the blots were subsequently hybridized to a glyceraldehyde-3-phosphate dehydrogenase (G3PDH) probe (Clontech, Mountain View, CA). The probes were radiolabeled by random priming with 32P-CTP. For quantification of the RNA blot analysis, the radioactivity of mRNA signals for MMP-2 was directly measured by a Bioimaging Analyzer, FUJIX BAS2000 system (Fuji Photo Film, Tokyo, Japan), and normalized relative to the corresponding G3PDH mRNA signals.
SDS-PAGE and immunoblotting of conditioned media were performed using a 5-15% gradient separating gel, Immobilon membrane (Millipore, Bedford, MA) and a mouse mAb to human MMP-2 (75-7F7, Fuji Chemical Industries, Takaoka, Japan) as described previously [23]. To quantitate the relative amounts of the MMPs, the bands on the film were subjected to image analysis (Adobe Photoshop). Statistical analysis was performed using Student's t-test.
Enzyme immunoassay (EIA)
The protein concentrations of pro-MMP-2 were measured using commercially available EIA kit (Daiichi Fine Chemical, Takaoka, Japan) using the protocols supplied by the manufacturer. All assays were performed in triplicate and statistical analyses were performed using Student's t-test.
Gelatinolytic activities in conditioned media were demonstrated using gelatin as a substrate. SDS-PAGE was performed under non-reducing conditions using a 9% separating gel containing 1 mg/ml gelatin. After electrophoresis, the gel was shaken gently in detergent buffer (5 mM CaCl2, 2.5% Triton X-100, and 50 mM Tris-HCl, pH 7.6) at room temperature for 60 min to remove the SDS, and then incubated in reaction buffer (0.15 M NaCl, 10 mM CaCl2, 0.02% NaN3, and 50 mM Tris-HCl, pH 7.6) at 37°C for 30 h followed by staining with 2.5% Coomassie brilliant blue in 30% methanol and 10% acetate. Enzyme activity was detected as a clear band on the resulting blue background of undigested gelatin. Gel images were analyzed digitally (Adobe Photoshop) to quantitate relative activities.
Effects of ECI with or without a chitobiose unit on MMP production by fibroblasts
Previous studies showed two important findings with regard to emmprin activity, namely that the activity resides in ECI [6], and that it depends on N-glycosylation of extracellular domains of emmprin [17,18]. These findings prompted us to synthesize the whole ECI with attached sugar chains (N-glycosylation). In the first step, ECI carrying one or two GlcNAc at Asn44 was synthesized. When added to fibroblast cultures, ECI-(GlcNAc)1 or 2 stimulated MMP-2 mRNA expression, while unsubstituted ECI had no stimulatory effect (Figure 2). The stimulatory activity of ECI-(GlcNAc)2 was much more than that of ECI-(GlcNAc)1 and was dose-dependent: approximately 1.1-, 3.6- and 4.6-fold stimulation at 7, 14 and 35 μM, respectively, compared to control. Stimulation was also demonstrated at the protein level. By immunoblotting, ECI-(GlcNAc)1 stimulated MMP-2 production by approximately 2.0-, 3.4- and 4.9-fold at 7, 14 and 35 μM, respectively, compared with the control, and ECI-(GlcNAc)2 stimulated it by approximately 6.7-, 7.2- and 8.6-fold, respectively, at the same concentrations (Figure 3). Again, unsubstituted ECI had no stimulatory effect. The stimulated production of MMP-2 protein by ECI-(GlcNAc)2 was also confirmed by quantitative EIA (Figure 4). ECI-(GlcNAc)2 significantly stimulated MMP-2 production (mean ± SEM, 114 ± 9.8 and 118 ± 8.6 ng/ml) of MMP-2 at 7 and 35 μM respectively, compared to control (9.1 ± 2.4 ng/ml) and ECI alone (14.2 ± 3.3 and 15.2 ± 4.1 ng/ml at 7 and 35 μM, respectively) (p < 0.01). The levels of MMP-2 stimulated with ECI-(GlcNAc)2 at 7 or 35 μM were similar to those stimulated in tumor cell-fibroblast co-cultures (124 ± 14 ng/ml).
Figure 2. Effects of ECI-(GlcNAc)1/2 on MMP-2 production by fibroblasts - Northern blotting. After culture of fibroblasts in the presence of synthetic ECI alone or ECI-(GlcNAc)1/2 for 3 days, the extracted total RNA was subjected to Northern blotting. Top panel, representative blots. Bottom panel, MMP-2 expression level relative to the control. Control-1, solvent control for ECI alone; control-2, solvent control for ECI-(GlcNAc)1 and 2.
Figure 3. Effects of ECI-(GlcNAc)1/2 on MMP-2 production by fibroblasts - western blotting. After culture of fibroblasts in the presence of synthetic ECI alone or ECI-(GlcNAc)1/2 for 3 days, the conditioned media were subjected to western blotting. Top panel, representative blots. Bottom panel, MMP-2 expression level relative to the control. Data are mean ± SEM (n = 3). Control-1, solvent control for ECI alone; control-2, solvent control for ECI-(GlcNAc)1 and 2. *p < 0.01, compared with the control.
Figure 4. Effects of ECI-(GlcNAc)1/2 on MMP-2 production by fibroblasts - enzyme immunoassay. After culture of fibroblasts in the presence of synthetic ECI alone or ECI-(GlcNAc)1/2 for 3 days, the conditioned media were subjected to enzyme immunoassay. Data are mean ± SEM (n = 3). Control, solvent control for ECI alone and ECI-(GlcNAc)2. *p < 0.01, compared with the control.
To rule out that (GlcNAc)2 alone stimulated MMP synthesis in fibroblasts, Asn-(GlcNAc)2 was added to fibroblast cultures. The results showed no stimulatory effect for Asn-(GlcNAc)2 or unsubstituted ECI on MMP-2 production (Figure 5), while ECI-(GlcNAc)2 stimulated MMP-2 production.
Figure 5. Effects of the control ECI peptide and the chitobiose unit on MMP-2 production by fibroblasts. The fibroblasts were cultured in the presence of synthetic ECI alone, Asn-(GlcNAc)2, and ECI-(GlcNAc)2 for 3 days, and the conditioned media were subjected to western blotting for MMP-2. Control, solvent control for Asn-(GlcNAc)2, ECI alone, and ECI-(GlcNAc)2.
MMP-2 stimulation activity of ECI-(GlcNAc)2 vs. ECI-[(Man)3(GlcNAc)2]
Next, we investigated whether ECI with longer chitobiose units could induce more potent stimulation of fibroblasts to produce larger amounts of MMP-2. Treatment with ECI-[(Man)3(GlcNAc)2] significantly stimulated fibroblasts to produce MMP-2 (98.7 ± 5.4 and 106 ± 11 ng/ml at 7 and 35 μM, respectively) compared to the control (24.4 ± 3.2 ng/m) (p < 0.01) (Figure 6A). However, the extents of stimulation by ECI-[(Man)3(GlcNAc)2] were lower than those by the same dose of ECI-(GlcNAc)2 (132 ± 7.8 and 138 ± 8.5 at 7 and 35 μM, respectively). The extents of stimulation of MMP-2 production by ECI-(GlcNAc)2 were almost similar to those by FU-EPS-1 tumor cell surface emmprin in co-cultures of FU-EPS-1 cells and fibroblasts (Figure 6B).
Figure 6. Effects of ECI-(GlcNAc)2 or ECI-[(Man)3(GlcNAc)2] on MMP-2 production by fibroblasts. A, After culture of fibroblasts in the presence of synthetic ECI-(GlcNAc)2 or ECI-[(Man)3(GlcNAc)2] for 3 days, the conditioned media were subjected to enzyme immunoassay. Data are mean ± SEM (n = 3). Control, solvent control for ECI-(GlcNAc)2 and ECI-[(Man)3(GlcNAc)2]. *p < 0.01, compared with the control. B, The conditioned media obtained as described above were subjected to gelatin zymography. At the same time, conditioned media from co-culture experiments of FU-EPS-1 tumor cells and fibroblasts were also applied to the same gel. Fb, fibroblasts. Fb control, fibroblast cultures with solvent control for ECI-(GlcNAc)2 and ECI-[(Man)3(GlcNAc)2].
Anti-emmprin blocking antibody Inhibits the MMP-2 stimulating activity of ECI-(GlcNAc)2 peptide
To confirm that the responses in the above ECI-(GlcNAc)2 peptide-induced stimulation of MMP-2 production were emmprin-mediated, inhibition assay using anti-emmprin blocking antibody was performed. EIA showed that the anti-emmprin blocking antibody inhibited (14 μM) ECI-(GlcNAc)2-induced stimulation of MMP-2 production (inhibition by approximately 58% at 10 μg/ml and 54% at 50 μg/ml), while non-immune IgG as control did not cause any inhibition (Figure 7).
Figure 7. Effects of anti-emmprin antibody on ECI-(GlcNAc)2-induced stimulation of MMP-2 production by fibroblasts. Fibroblasts were cultured in the presence of ECI-(GlcNAc)2 and anti-emmprin antibody or control non-immune IgG for 3 days, and the conditioned media were subjected to enzyme immunoassay for MMP-2. Data are mean ± SEM (n = 4). *p < 0.01, compared with the control.
The present study showed that the synthetic emmprin ECI peptide can exhibit emmprin activity to stimulate fibroblasts to produce MMP-2, when substituted with a chitobiose unit (GlcNAc-GlcNAc). The whole ECI without a chitobiose unit showed no stimulatory activity on MMP-2 production. These findings suggest that ECI is a key domain in determining the activity of the emmprin molecule. Moreover, the results showed that ECI was active, in terms of stimulating MMP-2 production, in the presence of the shortest form of N-glycosylation.
Two groups have reported that emmprin stimulation of MMP production in fibroblasts is dependent on N-glycosylation of its extracellular domains [17,18]. The ability of the emmprin molecule to participate in homophilic adhesion alone is not sufficient for MMP induction because glycosylation is not needed for homophilic adhesion but is essential for MMP-1 and MMP-2 induction [18]. ECI with glycosylation, although just a short chitobiose unit, may send a signal into the cells to upregulate MMP-2. There are two possibilities: First, the carbohydrate side chains may participate directly in ligand binding to a putative fibroblast receptor. Second, they may be necessary for preservation of an active molecular conformation [5]. Intriguingly, in our study, ECI substituted with only two GlcNAcs induced MMP-2 expression at both mRNA and protein levels. This chitobiose unit is the common structure formed at the reducing end of N-linked carbohydrates. Longer and more complex N-linked carbohydrates are reported to be involved in cellular adhesion, possibly via direct binding to lectins [26]. As for emmprin ECI, however, substitution with only two GlcNAcs was more potent than that with the core pentasaccharide. Thus, it is more likely that the chitobiose unit plays a role in preservation of an active molecular conformation. The peptide structures might be bent somehow by hydrogen bonds formed between amino acids and carbohydrates to form an active molecular structure. This possibility is currently under investigation in our laboratories. Similarly, it was shown that the adhesion domain of human CD2 bears a single N-linked carbohydrate, and that the carbohydrate stabilizes the protein fold by counterbalancing the unfavorable clustering of five positive charges centered about lysine-61 of CD2 [27]. Furthermore, the addition of short saccharides (e.g., di-, tri- and tetra-saccharides) to Notch by Fringe is postulated to increase Notch's sensitivity to Delta-like ligands, although they are O-linked carbohydrates [28]. This glycosylation supposedly does not affect Notch signaling by directly influencing the binding between Notch and ligands but may influence steps that occur just before the release of the Notch intracellular domain by proteolytic cleavages [28].
Induction of MMP-1, 2 and 3 mRNAs in uterine fibroblasts by non-glycosylated recombinant emmprin has been reported also [19], although a higher expression at the protein level was not confirmed. The authors hypothesized that their recombinant emmprin maintained the disulfide-stabilized tertiary structures, which let emmprin form dimers in solution and promoted their binding to the cell surface receptors, followed by increased MMP expression. Our study used smaller ECI peptides so that chitobiose substitution might have been necessary to give the peptide some tertiary structures. Moreover, the fibroblasts used in this study were stimulated to produce only MMP-2, but not MMP-1 and 3, in response to tumor cell emmprin (data not shown). Thus, the effect of the ECI peptide with chitobiose substitution on MMP-1 and 3 could not be examined.
Recently, the crystal structure of the extracellular portion of emmprin has been determined [29]. The structure comprises an N-terminal IgC2 domain (corresponding to ECI in this paper) and a C-terminal IgI domain, which are connected by a 5-residue flexible linker. This unique domain organization leads to overall flexibility and diverse dimerization manners of emmprin and may explain its multifunctional character. Another possible explanation for multifunction is glycosylation, since the latter is a highly diverse nontemplate-driven process that can generate enormous informational content [30]. The glycosylated form of emmprin was not analyzed in the above mentioned crystalographic study.
In this study, ECI was shown to stimulate MMP-2 production in the presence of the shortest form of N-glycosylation. On the contrary, we previously reported that ECI-derived peptides inhibit emmprin-enhanced MMP-2 production in the absence of N-glycosylation [11,24,31]. One of the ECI-derived peptides, emp#2, which contains a putative N-glycosylation site but shows no glycosylation, effectively inhibited emmprin-induced stimulation of MMP-2 production. Furthermore, emp#2 peptide effectively inhibited the enhanced invasion of matrigel by glioblastoma cells in the co-presence of fibroblasts [31]. These results also show biological importance of presence of N-glycosylation in ECI.
Thus far, several lines of evidence point to the importance of emmprin in cancer biology. First, emmprin is upregulated in a broad spectrum of malignant tumors, including carcinomas, gliomas and lymphomas, compared with their normal counterparts as mentioned in the Introduction section. Second, emmprin promotes tumor progression as well as upregulation of MMPs in animal models: emmprin cDNA-transfected human breast cancer cells were considerably more tumorigenic and invasive than plasmid-transfected cancer cells when implanted into the nude mouse [32]. Third, as already discussed above, emmprin may be responsible for upregulated MMPs, enhanced angiogenesis and hyaluronic acid production, transformation of stroma fibroblasts, and drug resistance [6,12-18,32]. In this context, it is important to elucidate the mechanisms involved in multifunctionality of the emmprin molecule.
This study indicates that ECI can mimic emmprin activity in terms of stimulating MMP-2 production by fibroblasts when substituted with chitobiose, the disaccharide with which N-glycosylation starts. This synthetic glyco-peptide may be useful for elucidating the mechanisms involved in glycosylation-mediated emmprin activities, which could lead to new strategies to prevent cancer invasion and progression enhanced by emmprin.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
TK, TS, HH and KK carried out the experiments. KN, HH, BPT, JS and AI participated in the design of the study, its coordination, and helped to draft the manuscript. In addition, technical guidance from YN and YO lead to successful experiments. All authors approved the final manuscript.
The authors thank Ms. M. Onitsuka for the skillful assistance in cell culture and co-culture experiments. This work was supported in part by a Grant-in-Aid for Scientific Research (No. 20590415) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, a grant from the Research Center for Advanced Molecular Medicine, Fukuoka University, and NIH grant CA082867.
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Originally written on NESN.com | Last updated 5/12/12
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subset: commoncrawl


text:
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text:
The Common Core State Standards for English Language Arts note robust expectations with regard to students' reading skills. While CCSS do not specifically suggest technology can play a role in helping students develop these skills, the increased access to computers and handheld devices in schools provides teachers with opportunities to tap into the array of digital resources focused on reading. Various free and inexpensive websites and apps can be used strategically to augment print resources, including with primary-aged learners. Sites designed for young learners require minimal technology skills beyond clicking a mouse.
Narrated Digital Text Sites
Students can access on hardware both at school and at home websites featuring digital text provide teachers with instructional resources at multiple reading levels. Several resources highlight text as words are narrated by a reader, a useful strategy for helping emerging readers. Narration allows students to access text at higher levels than they are able to read independently. Listed resources provide students with good models of fluent readers, especially since students can listen to the tone, pitch, and expression of the reader. The capacity to start, stop, and repeat passages provides differential support as needed for individual students, as do the visual cues provided at several of the sites.
In addition to the sites above, Storia is an e-reader that includes five free books with a complimentary Scholastic account. Additional books can be downloaded, costing between $1.99 and $7.99 each. Storia allows teachers to create a bookshelf for each child containing read-to-me and activities options based on the lexile level of each title. The PC version of Storia can be downloaded at the Scholastic website, and an iPad version can be downloaded at iTunes.
For informational texts, search for e-books at sites such as iTunes and Amazon by typing keywords related to content—such as "caterpillar." Some books are free for download, while others are minimally priced. Many e-books include features such as font size adjustment, link to a dictionary, and note taking options. Students can stop and replay e-book content as needed, and they can access the text with visual and audio scaffolds that help them develop phonological awareness, phonics and word recognition, fluency, and comprehension. English learners may especially benefit from using eBooks.
Text-Only Sites
While narration and visual cues can help students read text, there are times when the lack of such features may contribute to reading skill development. For example, assessments aligned with the Common Core State Standards sometimes ask students to highlight evidence from the text. Available digitized text allows them to practice this task under teacher direction. After copying and pasting text from a site, students can be prompted to change words in sentences in ways that evoke a different meaning, an activity that requires them to carefully analyze the content. They could also be asked to highlight all of the words that rhyme with one named by the teacher, or even search for words as they ponder key ideas and details about the passage. Such tasks help to develop skills in using a word processor as well as build reading skills.
Apps, programs for handheld devices such as iPads or iPods, can be downloaded from iTunes and other sites. Even a limited number of hardware can be used effectively as part of rotations through learning centers or as timers prompt students to deliver the device to the next student on a list. Different apps can be loaded on each device, providing students with activities based on their specific needs and learning levels. Many apps focus on comprehension more than other reading skills, so they complement the resources noted above nicely. Several of the resources provide the learner with immediate feedback and several track student progress, providing teachers with useful assessment information. The table below notes titles available for download worth exploring at iTunes.
There are many useful literary and informational online resources that teachers can implement effectively to develop skilled readers. In fact, suggesting some of the resources to parents can extend learning opportunities outside of the classroom, providing students with rich practice opportunities at home. The sites offer students materials that are interesting and interactive, keeping students engaged in the learning process at levels consistent with their personal needs. With a little creativity, even teachers with limited classroom technology can engage their students using web resources and apps, contributing to broad reading skill development.
Dawn Poole is a Professor of Educational Technology at California State University Stanislaus.
Whitney Donnelly is an Associate Professor of Teacher Education at California State University Stanislaus.
TILE-SIG Feature: Creating a Shared Vision for Personalized Digital Learning
TILE-SIG Feature: Learning with E-Readers in the Classroom


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El Gran Payaso
Joined: Apr 2006
Location: San Antonio
Oddometer: 9,120
A short day ends in a low-side...
Originally Posted by
Tricepilot, you kill me.
When are we gonna get to the crash?
Friday morning was a bright, beautiful day in Jalisco (state of) and everyone was looking forward to the ride to Puerto Vallarta, with a stop at Mascota for lunch.
I suppose looking back on it, there were several things I could point to that if I eliminated, I might have been able to not lay the bike on it's side just east of Mascota. But I didn't, and it happened, and press on we go...
Hundreds of motorcycles gather in downtown Guadalajara after checking out of the two main hotels that hosted the event.
Some folks initially talked about leaving for Mascota early and avoiding the crowds on the highway, but then others prevailed with the view that you rarely get to experience the rush that comes with parading out of a major Mexican city with police escort and that many bikes on the highway.
There were the ever-present hostesses ensuring that riders left with fond memories...
Not sure what's going on here with Davis, except to guess that he was hyperventilating with excitment before the mass departure...
Hank's GS with Ann on the back - these guys were in the lead pack, and riding two-up they were faster than most single riders
Alejo was said: "Once you crash, you will always think there is never enough gear in the world"
This guy was wearing an exoskeleton:
We took off out of Guadalajara in one large pack.
I was near the front of the parade out of town as we did some stop and go to clear the city, then out into the countryside.
Everybody kept decent distance and the pack was well-regulated. There was some passing and some fairly aggressive riding styles, but what do you expect with hundreds of riders and a little machismo here and there
Hank had fitted my GS with Ohlins shortly before the trip, and the new suspension helped glue to bike to the rails in the mountains.
Even rather packed down, the GS was "sticking" to the corners in the twisties.
There were literally two corners to go in the mountains before the lunch stop at Mascota, and I was right about here:
I was in a decending, left hand turn, going about 30.
A guy in a car coming opposite direction (from Mascota) sees rocks from the mountainside in his lane, and comes into my lane to avoid hitting the rocks in his lane:
I have to stand the bike up, out of the lean angle, to avoid the car and go around him.
As I pass him, I'm wide into the corner, and I press on the left grip to lean the bike back down to regain a corner line.
By this time, I'm into the marbles in the corner, and the rear tire breaks traction, and she low-sides.
To my right is a wall, that ends and then there is nothing but brush and a rocky cliff face. I slide past all of that on my left side.
The left side aluminum pannier busts apart, showering the road with its contents
The SPOT satellite messenger flies out of its mount, but is retained due to its tether.
The Zumo in its mount takes a rock to the face, and despite being chipped, did not fail to restart later.
The crash was a classic "slow motion in memory" crash in that even now I can remember it in frame-by-frame detail.
The effect of hitting the road I relate to a WWF wrestler picking you up, turning you sideways, and slamming you to the mat.
I slid to a stop on my left side/butt, about 50 feet from where the bike turned over.
There was debris from the pannier everywhere.
The guy in the car didn't even know what happened, I guess he turned the corner and went on his merry way, never seeing what happened.
I'll post pics next, but first a little contest.
Which of the following ATGATT pieces of gear took it the hardest??
(1) Helmet
(2) Gloves
(3) Jacket
(4) Pants
(5) Boots
Hint: you won't get it right the first time.
Collective Guide to Riding in Mexico
Off-Road Durango to Mazatlán
The Treasure of the Sierra Madre
Into the Blue at Quintana Roo
On Mexican Time
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CAUTERISING tumours with radio waves may provide a less invasive alternative to surgery for liver cancer and many other types of tumour, say two cancer specialists.
Surgery to remove a tumour can prevent cancer spreading throughout the body. But in some cases, doctors decide not to operate, perhaps because the tumour is too close to an artery or because the patient is too weak to survive the operation. Sometimes chemotherapy can be used to kill the tumour cells. But these drugs kill healthy cells, too, and can make the patient feel very ill.
So radiologist John McGahan and oncologist Philip Schneider of the University of California at Davis are developing another alternative treatment, which is known as radio-frequency ablation. It involves heating the diseased cells with a fine electrode, and is similar to the traditional technique for cauterising blood vessels. "Essentially, we are hard-boiling the tissue," says Schneider.
To treat ...
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Official: nV News Reviews the EVGA Geforce GTX 460 Superclocked
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nV News Alumni
Join Date: Sep 2002
Location: Finger Lakes of Hell, NY
Posts: 5,399
Page 7
Benchmark Results
Unigine Heaven
DX11, shaders at high
1920x1080, 4xAA/16xAF
Tessellation at Moderate
1920x1080, 4xAA/16xAF
Tessellation at Normal
This is an unexpected result. It would have seemed at first glance that the GTX 465's 256-bit memory bus would have out-tessellated the GTX 460, but the little 768mb card actually beat its larger sibling in the moderate test, and stayed within 1 fps in the normal test. The HD 5830 tried to keep pace but ran out of gas once a little more tessellation was used.
Stone Giant
1920x1080, 4xAA/16xAF
Tessellation at Medium
1920x1080, 4xAA/16xAF
Tessellation at High
Once again, the EVGA GTX 460 SC keeps pace with the 465, while outclassing the Radeon. The reconfiguration of the core and optimization of the SM units must be playing a role here.
3DMark Vantage
Performance Preset (1280x1024)
1920x1080, 4xAA/16xAF, Extreme textures, shadow shaders, shadows and shader quality, post processing scale at 1:5
Traditionally the Radeons have done better in this benchmark. It is interesting to see the 460 eclipsing the 465, again, especially in the GPU score for the 1920x1080 benchmark, as it also beats the HD 5830.
I don't understand why Radeons do so well in Feature Test 6. If someone can enlighten me, please do.
3DMark with PhysX Enabled Performance
It appears that although the GTX 460 is strong at PhysX, the 465 is a little bit stronger for the most part.
D3D11 SDK Detail Tessellation Demo
1920x1080, 4xAA/16xAF
Detail Tessellation
Texture: Rocks
Displacement selected
Tessellation Factor (edges): 11.00
Tessellation Factor (inside): 11.0
Link Tess. factors selected
Rotating camera selected
In this test, things line up a little closer to how the specs line up, with the GTX 460 lining up firmly in between the GTX 465 and HD 5830.
D311 SDK SubD11 Demo
1920x1080, 4xAA/16xAF
Patch Division: 10
Bumpheight: 0.15
Toggle Materials
This demo makes heavy use of tessellation as well. The bump height adjustment adjusts the amount of displacement mapping (no real effect on performance), and the patch divisions setting adjusts tessellation. Worth noting is that on both the GTX 460 and 465, adjusting tessellation all the way up to setting 31.0 only brings performance down into the thirties, whereas the Radeon is already in the thirties at 0.15.
NVIDIA Human Hair Demo
1920x1080, 4xAA/16xAF
Presets 3
Animation 3
Curly Hair, shadows, HW tessellation, Dynamic LOD selected
Play Animation
Loop Animation
Shadows selected
LOD rate at default
Add wind force, wind strength at max, wind randomness at max
Smoothing interval at default
Compute shader and simulationLOD selected
Show floor, show face, show floor shadows selected
... Another tessellation-heavy demo that is just too much for the Radeon. The GTX 460 and 465 run this test almost identically.
Gameplay Benchmarks -
Metro 2033
SP Mission: "Bridge"
"High" Preset, 1280x720, 4xAA/16xAF, DX11 on, Advanced DOF off
"High" Preset, 1920x1080, 4xAA/16xAF, DX11 on, Advanced DOF off
This game shows tessellation in action, amongst a host of other system-taxing effects. What's VERY surprising is that the EVGA GTX 460 SC manages to perform on-par with the GTX 465 in this game, sometimes beating it. It's reasonable to infer that at these settings the game would be very fluid at 1920x1080with no AA and a little bit of AF. Predictably the Radeon falls short in this game.
"Ultra" Preset, 1280x720, 4xAA/16xAF
Custom track run without AI opponents
1920x1080, 4xAA/16xAF
This game uses a little bit of tessellation as well, not enough to over-tax the Radeon. All three cards remain competitive in all tests, but surprisingly the GTX 460 pulls a solid win in both resolutions.
Battlefield: Bad Company 2
Single player mission 1
All settings at highest, DX11, HBAO on
1280x720, 4xAA/16xAF
1920x1080, 4xAA/16xAF
The only DirectX 11 feature used in this game is soft shadow, which aren't very system-intensive. Since the release of this game, however, Radeon cards have always run this game quite a bit better. NVIDIA has told me that they are currently working on performance improvements for this game.
Dark Void
Jetpack jungle runthrough
All settings at highest, Physx OFF
1280x720, 4xAA/16xAF
1920x1080, 4xAA/16xAF
I have tested and retested this with all cards, getting the same result every time. This could just be a matter of where I'm at in the game; it might be a spot where the Radeon has an edge somehow. I may just drop this benchmark, or find another gameplay example that doesn't show such disparate performance.
Far Cry 2
1280x720, 4xAA/16xAF
Demo(Ranch Medium), 1280x720 (60Hz), D3D10, Fixed Time Step(No), Disable Artificial Intelligence(Yes), Full Screen, Anti-Aliasing(4x), VSync(No), Overall Quality(Custom), Vegetation(Very High), Shading(Ultra High), Terrain(Ultra High), Geometry(Ultra High), Post FX(High), Texture(Ultra High), Shadow(Ultra High), Ambient(High), Hdr(Yes), Bloom(Yes), Fire(Very High), Physics(Very High), RealTrees(Very High)
1920x1080, 4xAA/16xAF
Demo(Ranch Medium), 1920x1080 (60Hz), D3D10, Fixed Time Step(No), Disable Artificial Intelligence(Yes), Full Screen, Anti-Aliasing(4x), VSync(No), Overall Quality(Custom), Vegetation(Very High), Shading(Ultra High), Terrain(Ultra High), Geometry(Ultra High), Post FX(High), Texture(Ultra High), Shadow(Ultra High), Ambient(High), Hdr(Yes), Bloom(Yes), Fire(Very High), Physics(Very High), RealTrees(Very High)
All of the cards remain competitive through all the tests for this game, with (surprise!) the GTX 460 coming out on top.
Resident Evil 5
RE5 Variable Benchmark, all settings at highest
64-bit HDR (ARGB16F) tweak
1280x720, 4xAA/16xAF
1920x1080, 4xAA/16xAF
This MT Framework-engined game looks great, runs wonderfully on the NVIDIA hardware, and runs adequately on the ATI card. Once again the GTX 460 is right at the heels of the GTX 465.
Lost Planet
DX10, all settings at highest
1280x720, 4xAA/16xAF
1920x1080, 4xAA/16xAF
Using the same engine as Resident Evil 5, I thought this game would show a similar result with ATI bringing up the rear. That didn't happen, and all three cards ran the game exceptionally well in most spots except for some serious choppiness in some of the snow areas at 19x10. This game is still quite taxing even to a newer PC.
Gameplay Summary
I did not expect the EVGA GTX 460 to do so well vs the GTX 465. In almost every game and benchmark it either comes close to matching it, or it wins altogether. Being the least expensive card of the group, the GTX 460 represents the best value. NVIDIA claimed that the GTX 460 was powerful in DirectX 9/10 games, and that it could play the toughest DirectX 11 titles. They made good on their word.
NOTE: I will be looking into the Dark Void issue over the following week, and despite being a total PhysX noob, I'm going to try to look into some of the PhysX aspects of some of the games I have (Dark Void, Mirror's Edge, Metro 2033) and see if I can add anything worthwhile to this review regarding this API.
Last edited by ragejg; 07-15-10 at
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Most athletes would agree.
"To the criminal element, anyone with money and fame is a target," Scott said.
"Away from football we try to be regular people, go out and have a good time," Gaffney said. "But eyes are always on us and sometimes people want what you have and they try to get it."
In September 2000, the Boston Celtics' Paul Pierce survived a brutal multiple stabbing at a Boston nightclub. Pierce is now licensed to carry a concealed weapon, but leaves his gun at home and hires a bodyguard when he goes out. Still, Pierce considers himself a target.
"Because I'm recognized from TV, people want what I have," Pierce said. "You have to be careful because people out there in the world are very envious of your life."
But some players don't agree that an athlete's high profile makes them a target in society.
"I don't know what you need a gun for in the NBA," former Utah Jazz star Karl Malone said in disbelief. "What are you doing that you want a gun? Who have you pissed off that you need a gun?" Malone's eyes grew bigger and he shrugged his shoulders, apparently confused at the reasoning behind athletes' fear of being attacked.
Malone is hardly anti-gun. An avid hunter, Malone even has been a spokesman for the National Rifle Association. But he rejects the argument that athletes need guns for protection.
"I think it's just a smoke screen, just an easy reason to say you want a gun," Malone said.
While Malone supports the constitutional right to bear arms, he said he is skeptical of the average athlete's mentality when it comes to firearms.
"Everybody sticks their chest out now when they have a firearm on them," Malone said, mocking the thought process of the common athlete. "'I come up from the hard part of the streets, the mean streets, and I need my gun and all of that?' Come on, please, enough of that already. We're tired of that."
Malone said he wants athletes to realize the dangerous nature of guns.
"Now why do these guys carry guns? Is that the 'cool' thing to do? Well 'cool' gets you dead!" Malone said.
"I know there is probably somebody out there who's carrying a gun because it makes him feel like more of a man," Williams said truthfully. "You don't carry a gun just to make you feel like you are big-time. That's the wrong reason to carry."
For athletes who claim they need a gun for protection, Malone has a suggestion: stop hanging out in places of risk.
"Three a.m.? My goodness gracious, what were you doing out at 3 o'clock in the morning? Who were you with? Where were you at? Do you need a gun to protect you or do you need a babysitter to get you where you need to be all the time so that you don't get in any trouble?" Malone said.
Malone said he thinks the problems stem from the people athletes sometimes keep as company, and the places they spend their free time.
"You can enjoy yourself in nice places, but we're talking about gun stuff," he said. "We need to talk more about where we are going, what we are doing, and who we are hanging out with that lead up to these confrontations."


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Time to once again introduce you to a Van Andel Living Shores resident, and this week I've chosen our California moray eel. He has one of the more interesting back stories. A gentlemen who conducted education programs with live animals had decided to leave Michigan, and was looking to place his marine specimens. While he was located in the Detroit area, we were the only facility in Michigan dedicated to coldwater fish and invertebrates. We were also given some sea stars and our swell shark (the pudgy brown one you MAY have seen in the kelp tank - more about her another time). Anyway, he had rescued Eel Young (I didn't name the eel by the way, although it is the sort of thing I might do. I was sure such a big and charismatic animal probably had a name already, and made a point of asking before we left) sixteen years earlier from an Asian restaurant in San Francisco where he was destined to become a meal. Eel Young has been here at JBZ five years now, making him at least twenty-one.
Morays are considered true eels because they lack pectoral and pelvic fins, as well as gill covers, making them very snake-like in appearance. Since he doesn't have covers to move the water across his gills, Eel Young must hold his mouth open and "gasp" in order to breathe. This can give him a rather frightening appearance, especially coupled with his mouthful of sharp little teeth, but morays are typically shy and unagressive. Having said that, they're a good reason to never stick your hand in a crack or crevice while scuba diving (Ever see that movie "The Deep"? Yikes!). If you ever watch the rockfish in our Kelp Tank eat you'll notice that they do so by opening their mouths wide to create a sort of vacuum that literally sucks the food in. Not an option when wedged in a cave. But Eel Young and friends have an adaptation that allows them to eat in the tight spaces where they hunt and hide: a second set of jaws at the back of the mouth that literally pull prey toward their throats. How cool is that?
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I've been adopted! I'm so happy!
Hey there! I am soooo happy to meet you! My name is DooDa, yup, just like Zippity DooDa.
I am such a cute and active little bunny. Very busy. So busy in fact that it was hard for Marcy to get a good photo of me. Haha---made her work for it!
Anyway, I am grateful to be at SaveABunny because I was recently scheduled to be euthanized at a local shelter since there was no room for me.
Too many people had abandoned their bunnies at the shelter and there just wasn't any room or time left for me. I met a really nice SaveABunny volunteer named Lily who became my advocate and she helped Marcy juggle spaces, so that I could be saved. I am very happy to be alive. I have so much energy and enthusiasm. It would have been sad for a bright light like me to go out.
Please adopt from shelters and rescues rather than at pet stores.
You'll save precious lives like mine.
Hope to meet you soon!
"Reflection Of Compassion" is a lovingly commissioned series of original watercolor and gouache illustrations created especially for SaveABunny Rabbit Rescue by artist Elizabeth Koval Maffeo. (All images copyright 2008 SaveABunny. All rights reserved.)


text:
You are hereHome › Dennis Faas › Freeware MP3 volume Normalizer?
Freeware MP3 volume Normalizer?
Have you ever turned your computer speakers loud enough to hear some of your favorite .MP3s in another room -- only to come rushing back to your computer to turn the volume down because the next song playing is just too loud?
That's what happened to me today. And with that in mind, I pondered whether or not there existed a freeware program that could normalize the volume of all my MP3s.
As usual, I headed over to Google for the answer. I searched for "freeware mp3 normalize" and managed to find a fantastic little program called MP3Gain. From the Webattack.com web site:
" MP3Gain analyzes and adjusts mp3 files so that they have the same volume. The program does not just do peak normalization, as many normalizers do, but instead attempts statistical analysis to determine how loud the file actually sounds to the human ear. The changes MP3Gain makes are completely lossless, there is no quality lost in the change because the program adjusts the mp3 file directly, without decoding and re-encoding. "
I downloaded the file onto my computer and installed it. In the main MP3Gain window, I had an option to choose which folder of MP3s I wanted to change. I opted for my Dean Martin folder and MP3Gain loaded in all the songs.
At this point, I couldn't figure out what to do next and ended up right-clicking over top of one of the MP3 filenames, where MP3Gain gave me the option to "Apply Track Gain". From there, I figured that I needed to highlight all of the files in the MP3Gain Window and then Apply the Track Gain... which ended up doing the trick with a normalized volume level of 89.0 db.
Overall, the application was relatively straight forward and did exactly what I wanted it to. Highly recommended!


text:
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Results 1 to 13 of 74
Thread: Black Tea´s
February 27th, 2011 #1
Black Tea´s
Hi everyone, my name is Wil, i`ve been drawing since i was a lil kid but only recently started studying seriously, i`m selftaught. I`ve been lurking around conceptart for quite some time admiring the great artists around here, and i finally decided it was time to start a sketchbook, for the purpose of improving, of course, so i will greatly appreciate any tip of advice you can give me.
So today i will be posting some face studies, and i`ll update this sketchbook as often as i can, so i`ll thank any feedback you can give me from now on.
Last edited by Black_Tea; August 22nd, 2012 at 07:24 PM.


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Originally written on Red's Army | Last updated 11/15/12
Last night Rajon Rondo rolled his ankle while wearing a pair of Nike Air Max 360 BB Low sneakers. This model is no longer in production by Nike, however Rondo has inexplicable decided to wear this shoe the past two games. I know rolling your ankle is a common injury in the NBA, however this particular shoe was the same model that Rajon injured himself in on March 14th of 2011. . The Nike Air Max 360 BB Low features a full length Air Max cushioning system. I own a pair of these shoes and they are incredibly comfortable, however the shoe lacks ankle support and lateral stability. The 360 cushioning system does not lend itself to Rondo's quick cutting style. Take a look at this picture of Rondo from last years All Star weekend. Pic via Counterkicks.com Is this a case of coincidence or is should Rondo put the BB Lows to rest?
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Illinois @ Arizona State NCAA Football Pick
- Updated: September 7, 2012
College Football Picks
Illinois Fighting Illini
Arizona State Sun Devils
Date/Time: September 8th, 10:30 pm EST
Television: ESPN
College Football Odds from BetDSI
Point Spread: Arizona State -4
Total: 48
Football Betting Game Trends
Illinois Fighting Illini
- Illinois is 2-6 SU in its last 8 games
- The total has gone UNDER in 5 of Illinois's last 5 games
- Illinois is 6-17 SU in its last 23 games on the road
- The total has gone UNDER in 5 of Illinois's last 6 games on the road
Arizona State Sun Devils
- Arizona State is 1-5 ATS in its last 6 games
- Arizona State is 1-5 SU in its last 6 games
- Arizona State is 7-2 SU in its last 9 games at home
NCAA Football – Week 2
The Arizona State Sun Devils and Illinois Fighting Illini both got off to great starts with their 2012 campaigns last week, posting wins and covers. One will move to 2-0 on Saturday night in one of the last kickoffs of the day when they meet at 10:30 ET in the desert in college football betting action.
QB Nathan Scheelhaase came to Illinois with a ton of promise to be the future of this team. Matters really haven't panned out all that well through two years and a game, but at least he still is showing signs that he has a ton of talent. Scheelhaase didn't have to do all that much last week against the Western Michigan Broncos, but he threw for 126 yards and rushed for 21 more, accounting for a TD on the ground and one through the air. With RB Mikel LeShoure gone though, there is a real hole at running back, where there are a number of players that are looking to take over as the featured back. None really stood out against Western Michigan, and that problem clearly is going to carry over to here in Tucson as well.
Last year was supposed to be the campaign in which Arizona State competed for the Rose Bowl. Head Coach Dennis Erickson knew that he had to get the job done, or he was going get axed, and losing the final five games of the season, including the bowl game to the Boise State Broncos just wasn't enough. Now, it is up to Head Coach Todd Graham to get the job done. He got off to a good start against the Northern Arizona Lumberjacks last week, winning 63-6 here at Sun Devil Stadium, a game that was 42-0 at the intermission. New QB Taylor Kelly, taking over for the departed QB Brock Osweiler, threw for 247 yards on 15-of-19 passing in the opener, and he also got some great contributions from RB Marion Grice, who had 14 carries for 107 yards and three scores. Granted, as is the case with a lot of these teams that looked impressive in Week 1, it was only the first week of the year, and the first opponent was a lowly FCS school that never should have had a chance of sticking around. ASU only did what it was supposed to do. This is a significantly tougher test.
Last year when these two teams met, Illinois was able to pull off the modest upset in Champagne. With this game being played in the desert though, many will think that it is time for revenge. The four-point spread seems to be just about right to us, but we think that this could be a game in which both teams struggle to move the football. Remember that Illinois only scored 17 points offensively last week against Western Michigan, and there isn't a team in the MAC with a good defense. Expect to see this one stuck in the low-40s. Arizona State 23 – Illinois 17
Adam Markowitz
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- NHL Betting Goalie Report for 1/31/2014 - February 3, 2014
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Converteam India Private LimitedGurgaon, Haryana
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Converteam has two main entities in India: Converteam India near Delhi and Converteam EDC near Chennai. To back our strategic development, in 2007 we opened a sales and projects office in Gurgaon near Delhi to strengthen our positioning in a very fast-growing marketplace. EDC was created at the beginning of 2005 to provide global technical support to Converteam units in automation, power systems, software, drafting and other support services. An International ...view all
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Halo impressions thread
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Angel Arms
Join Date: Oct 2002
Location: Rockford, IL
Posts: 624
Originally posted by saturnotaku
I believed Halo would be a game that would take us back to its roots - to where Bungie had intended during the PCXL screenie days. It sounded like Gearbox was going to take great care to make sure the game was done right, and I know I'm not the only one here who has been more than a little disappointed by the results. You say they're working on it, well they've been working on it for almost two years now. I'm frustrated at Gearbox, I'm frustrated at Microsoft, I'm frustrated at the continued prevalence and sub-par quality of console ports. And I'm saddened that Halo has to be put in that category, especially after we waited so long.
This may sound contradictory, but, Amen! I honestly, deeply wish that Bungie hadn't been bought out. That's the root of the design flaws that we see in Halo. The stuff that they were talking about doing during the original PC development was mind-blowing. Still is.
I'm not going to put Halo in the sub-par category... par for console ports seems to me to be right in the middle of the crap pile. Vice City is definitely a well-done port. But Halo's also much better than any one of the slew of high profile console ports that have come out - Metal Gear Solid 2: Substance, Metal Gear Solid, Spiderman: The Movie, and Enter the Matrix jump to mind.
And you know, I'm more disappointed with the SP than I thought I would be. I don't really care, though. It was worth going through just for the experience - the MP justifies the purchase of the game for me. I wish your broadband situation was more ideal; taking people apart in CTF would be easier if I had someone who I knew on my team.
Simply choosing to program to construct your entire game to take advantage of one archetecture gimps you if you end up moving it to a dissimilar archetecture that has no hardware standards whatsoever. Instead of starting from scratch and building something that can run on many different configurations and then picking one and running with it, you're picking the one way that's efficient and powerful to do things on this platform, and then trying to tack on additional functionality afterwards. It's the difference between using a powered screwdriver to get a screw out of a wall and using the blade of your pocket knife to achieve the same task - both will do the job, but one was designed specifically for the job while the other is doing multiple jobs that it wasn't necessarily designed for.
Yeah, I think that Halo started development Christmas 2001 - you're right. This was still plenty after Halo PC was released for the Xbox. Gearbox has had it for a long time - but I think that a lesser company would have churned out something that was a lot worse.
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About Cetaceans
Cetaceans are marine mammals with streamlined (hydrodynamic) bodies that glide easily through their watery environment, horizontal flukes, front flippers for steering and a layer of blubber directly under the skin. According to the Society for Marine Mammalogy, 90 species of whales, dolphins, and porpoises are included in the Order Cetacea.
Cetaceans Frequently Asked Questions
How big is a blue whale's heart? Do whales have hair? These questions and many more are answered.
A page devoted to the characteristics of the four species of this family (North Atlantic Right Whale, Southern Right Whale, North Pacific Right Whale, and Bowhead Whale)
This family, also known as the 'rorquals,' includes the humpback whale and the blue whale
What is the difference between a dolphin and a porpoise? Find out by comparing this family to the delphinidae
Physeteridae and Monodontidae
Species in these two families include the beluga, the narwhal, and the largest toothed whale in the world


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Review: MacAlly LINK360-U
A great gift and travel accessory for iPod (December 15th, 2005)
MacNN Rating:
Product Manufacturer: MacAlly
Price: MSRP $19.99 US
The Good
- Easily connect your iPod without undo gymnastics. Flexible connector.
The Bad
- Only for the iPods with 30-pin dock connector. USB 1 only.
In the course of a day my trusty iPod is plugged into several different computers as I update, repair, or backup my clients' machines. My iPod Photo 60GB serves as a backup device and even an emergency start-up drive. Sometimes it is a strain to stretch and reach connectors while connecting the iPod to a computer under a desk, and I wish that there were more connector flexibility. MacAlly has a great solution with a new line of adapters that are designed to allow you to easily connect your iPod to a computer. These are small products with the less flexible in mind.
Strech and SwivelThe Link360-U, designed for all dock-connecting iPods, has a 3-dimensional swivel 30-pin to USB adapter. It even comes with a 4 foot USB extension cable. The product is named for a patented neck that allows you to rotate the adapter in a complete circle to meet a wide range of angles. A thick metal ring between the two parts houses the rotating mechanism. Both sides of the adapter swivel, which makes snaking around the back of a computer much easier. The swiveling neck seems durable, but I'm sure that overly harsh twisting might injure it.
This is a handy adapter for a traveling kit because it only weighs .3 ounces. It is a very useful gift for anyone who works on multiple computers. A FireWire 400 version (LINK 360A) will be available soon. The LINK360U is covered by a one-year warranty and can be purchased directly from MacAlly's site.
Edited by Ilene Hoffman, Reviews Editor


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1859 P50C Half Dollar, Judd-242, Pollock-298, R.5, PR65 ...
2004 Orlando, FL (FUN) Signature Sale #336
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Lovingly Preserved Gem 1859 Half Dollar, Judd-2421859 P50C Half Dollar, Judd-242, Pollock-298, R.5, PR65 Brown PCGS. The Longacre design for the half dollar that features a bust of Liberty facing right, draped with a ribbon inscribed LIBERTY with a wide wreath of oak and vine on her head. The reverse has the denomination 50 CENTS within a wreath of cotton, tobacco, sugar cane, corn, wheat, and oak. Struck in copper with a reeded edge. The obverse retains traces of red color, although mahogany-brown patina dominates both sides. A sharply struck and beautifully preserved Gem. Population: 3 in 65 Brown, 1 finer (10/03).
From the Frank O. Fredericks Collection, Part III. (#11980) (PCGS# 11980)
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text: What do you look for when commissioning a photographer? Creativity, empathy, professionalism, a genuine desire to please and of course fabulous photographs that capture the essence of your event? Dan Tyack, a photographer working in Manchester and throughout the North West has all of these qualities. His aim is to ensure that his clients are delighted, not only with the end result – stunning photography with the WOW factor - but with the whole experience.read more


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Show details
Special agents investigate crimes related to the Navy and Marine Corps.
Mark Harmon, Michael Weatherly, David Mccallum, Pauley Perrette, Sean Murray, Rocky Carroll, Brian Dietzen, Emily Wickersham, Cote De pablo, Lauren Holly, Sasha Alexander
Gary Glasberg (Executive Producer), Chas. floyd Johnson (Executive Producer), Mark Horowitz (Executive Producer), Mark Harmon (Executive Producer), Shane Brennan (Executive Producer), Donald Bellisario (Executive Producer), James Whitmore jr. (Director), Shane Brennan (Writer), Tony Wharmby (Director), Nicole Mirante-matthews (Writer), Gina Monreal (Writer), Gary Glasberg (Writer), Scott Williams (Writer), Dennis Smith (Director), Jennifer Corbett (Writer), George Schenck (Writer), Frank Cardea (Writer), Arvin Brown (Director), Steven Binder (Writer), Tom Wright (Director), Christopher Waild (Writer), Holly Dale (Director), Terrence O'hara (Director), David j. North (Writer), Bethany Rooney (Director), Christopher Silber (Writer), Rocky Carroll (Director), Alrick Riley (Director), Leslie Libman (Director), Donald Bellisario (Writer), Christopher Walid (Writer), James Whitaker (Director), Bradford May (Director), John c. Kelley (Writer), Alan Levi (Director), Darcy Meyers (Writer), Chas. floyd Johnson (Producer), John Tinker (Producer), Mark Horowitz (Producer), Bill Nuss (Writer), Michael Weatherly (Director), Mario Van peebles (Director), Frank Cardera (Writer), Reed Steiner (Writer), Mark Horowitz (Director), Allison Abner (Writer), Terrance O'hara (Director), Michelle Maclaren (Director), George Schneck (Writer), Jesse Stern (Writer), William Webb (Director), Andrew Bartels (Writer), Kevin rodney Sullivan (Director), Steven Kriozere (Writer), George Schenck (Director), Frank Cardea (Director), Dennis Smith (Writer), Craig Ross jr. (Director), Mark Horowitz (Writer), Jesse Stern (Director), Lee david Zlotoff (Writer), Terence O'hara (Director), Dan e. Fesman (Writer), Alfonso h. Moreno (Writer), Linda Burstyn (Writer), Oz Scott (Director), Colin Bucksey (Director), Martha Mitchell (Director), Jeff Woolnough (Director), Jack Bernstein (Writer), Dana Cohen (Writer), Don Mcgill (Writer), Nell Scovell (Writer), Ric Arthur (Writer), Robert Palm (Writer), Dana Coen (Writer), Laurence Walsh (Writer), Richard Arthur (Writer), Stephen Cragg (Director), Aaron Lipstadt (Director), Gil Grant (Writer), Michael Zinberg (Director), John Tinker (Executive Producer), Donald Bellisario (Director), Frank Military (Writer), Steve Kane (Writer), Alan j. Levy (Director), Frank Wright (Director), Juan carlos Coto (Writer), Peter Ellis (Director), Ian Toynton (Director), Philip Deguere jr. (Writer), Roger Director (Writer), Roger Director (Director), Jeff Woolnough (Writer), Thomas l. Moran (Writer), Frank Careda (Writer), Bob Gookin (Writer), Jeff Vlaming (Writer), Larry Moskowitz (Writer), Christopher Crowe (Writer)
|"Heartland" When a murder investigation leads the team to Gibbs' hometown, secrets about his past are revealed. (Repeat)
|"Murder 2.0" A murderous psychopath taunts the team by leaving clues to the next victim's identity during the week of Halloween. (Repeat)
|"Check" The team investigates a series of crime scenes that appear to be copycats of previous cases; two of Gibbs' ex-wives show up at a crime scene. (Repeat)
|"Check" The team investigates a series of crime scenes that appear to be copycats of previous cases; two of Gibbs' ex-wives show up at a crime scene. (Repeat)
Naval Criminal Investigative Service Special Agent Leroy Jethro Gibbs leads a group of colorful personalities in investigating crimes -- ranging from murder and espionage to terrorism -- that have evidence connected to Navy and Marine Corps personnel. The team includes witty ex-homicide detective Anthony DiNozzo, quirky forensics specialist Abby Sciuto, and the brilliant -- if insecure -- Timothy McGee. Dr. Donald ``Ducky'' Mallard brings his vast experience in forensics into play to help solve cases.
Current cast
Mark Harmon as NCIS Special Agent Leroy Jethro Gibbs
Michael Weatherly as NCIS Special Agent Anthony Dinozzo
David Mccallum as Dr. Donald ``Ducky'' Mallard
Pauley Perrette as Forensic Specialist Abby Sciuto
Sean Murray as NCIS Special Agent Timothy McGee
Rocky Carroll as NCIS Director Leon Vance
Brian Dietzen as Jimmy Palmer
Emily Wickersham as NSA Analyst Eleanor ``Ellie'' Bishop
TiVo subscribers who like "NCIS" also like...
Program data from Tribune Media Services, Inc.


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Hear the difference.
Chassity Hancock graduated from Auburn University with a Bachelor of Science in Communication Disorders in 1997. In 1999, she graduated from Auburn with a Master in Audiology, and completed an externship at Vanderbilt University Medical Center. She is a Fellow of the American Academy of Audiology, is licensed in audiology by the Alabama Board of Examiners for Speech Language Pathology and Audiology, is a member of the American Speech Language Hearing Association and holds a Certificate of Clinical Competency. She has worked for North Alabama ENT since April 1999.
Board Certification: General Otolaryngology - 1998
Undergraduate: University of Michigan
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Robin Hanson is really on fire now with his analysis of farmer vs. forager psychology. Whether consciously or not, he's extending the farmer model given by Cochran and Harpending in The 10,000 Year Explosion. Cochran and Harpending's model is interesting in the way it points out the disappointing truth about humanity's self-domestication. To put it in crude terms, we've naturally selected ourselves into a bunch of conformist townie wussies.
My default model of Homo sapiens is four-layered — our primate-mammalian background from 80 mya, the Homo sapiens EEA (environment of evolutionary adaptiveness) pan-species bedrock, post-African diaspora/farming/Neolithic Revolution selection pressures, and the modern world. Rich data is available to update the model at all four levels, but in my opinion #3, the farming revolution, is most neglected. I hazard to guess it's the most neglected because the particulars of it make distinctions between different groups of existing humans.
Another neglected area, as far as my reading goes, is the mystical/mythical side of the time period intermediate between the EEA and farming. The period of time when all our elaborate myths were invented, perhaps 10-20,000 years ago. The Golden Bough provides powerful evidence of the content of this entire area (hint: it involves burning lots of effigies), but what scholarly work exists on mythological origins prior to all trendy modern traditions? The Golden Bough was published 120 years ago. Anyone know more recent material?


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U of M sees development as a windfall
Partnership could bring millions by Highland renovation project
A private development firm and the University of Memphis have billed a new construction project on the Highland strip as a revenue generator -- with the potential to draw $130 million in investment to the area and about $26 million in new tax revenues over the next three decades.
The mixed-use redevelopment would renovate two blocks on Highland south of Central, adding more than 200 apartments, town homes and retail space.
But there's a twist to the $63.5 million project, which will be presented to Shelby County commissioners today.
The developers, Poag & McEwen and the U of M, have submitted a plan that would rely on a creative private public partnership called "tax increment financing" to finance about $10 million to $12 million of the project.
Known by its acronym, TIF has been used by such cities as Nashville and Chicago to redevelop blighted areas by issuing bonds to pay for the cost of rebuilding infrastructure.
Yet, while the funding method was recently used to help finance the Uptown Redevelopment Project, its use is rare in Shelby County.
"We've never used tax increment financing for a development like this," said commission chairman David Lillard.
The way it works is local governments identify blighted areas in need of redevelopment and freeze property taxes in the area.
Public bonds are then purchased to fund the costs of rebuilding infrastructure, such as parking lots and sidewalks.
The idea is that private developers will be lured by the improved infrastructure and will invest in new building projects, improving property values.
As the property values in the area go up, that increases tax revenue, which goes to pay off the original bonds.
U of M and Poag & McEwen have gone in on the application together, with the private firm developing about half of the area, and the university adding another $18 million for new buildings, including a new alumni advancement center.
In an initial report submitted by the developers to the Memphis and Shelby Community Redevelopment Agency, about $12 million of the plan would be funded by publicly issued bonds.
These funds will be used to make sidewalk improvements, add street lights, fund demolition in the area and build a new parking garage, according to Bob Rogers, a senior vice president and general counsel for Poag & McEwen.
Rogers said it will take about 20 to 25 years to repay the bonds.
The parking garage would replace the Highland Street Church of Christ, 443 S. Highland, which plans to move to Houston Levee and Walnut Grove.
In order to qualify as a TIF district, by state law the area had to be designated as either blighted, a slum area or lacking adequate affordable housing.
According to a Community Redevelopment Agency report, the area was deemed blighted due to unsanitary or unsafe conditions, a faulty lot layout, deterioration of site improvements and inadequate parking facilities.
The same report also showed that CRA staff viewed the "degree of blight may or may not be deemed 'predominate or substantial.'"
Yet the CRA's board approved the project in September anyway.
That designation doesn't have County Commissioner Mike Ritz convinced, however. "I don't buy into that," he said. "If Highland strip is a blighted part of Memphis, then you could call almost anything blighted."
Last week the project was approved in committee by the City Council. Today the County Commission will take a look at three resolutions and a joint ordinance that will pave the way for the creation of a TIF district.
Ritz said he's not comfortable using public dollars to help fund private development.
"In this particular case, what they want us to do is to borrow public money, issue debt, and give the money to them for a parking garage to support their development," Ritz said.
"Why subsidize high-rent housing and retail development? ... The taxpayers are getting ripped off."
-- Alex Doniach: 529-5231
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Journal of Spinal Disorders & Techniques, 04/04/2012
Cage design and position do not significantly affect failure of the construct or stiffness in compression across the endplate. Bone mineral density significantly affects both failure forces and stiffness but is not dependent on the positioning or design of the cage.
© 2015 M3 USA Corporation. ALL Rights Reserved.


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SD57045-01 Transistor, N-CHANNEL ENHANCEMENT-MODE LATERAL MOSFETs
The SD57045-01 is a common source N-Channel Enhancement-Mode Lateral Field-Effect RF power transistor designed for broadband commercial and industrial applications at frequencies up to 1.0 GHz. The SD57045-01 is designed for high gain and broadband performance operating in common source mode at 28V. It is ideal for base stations applications requiring high linearity.
MFR: ST Micro
Limited Quantity Available


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Results 1 to 4 of 4
Thread: Please critique
June 23rd, 2012 #1Registered User
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Please critique
Hey, I'm relatively new to digital art and I really haven't had any constructive criticism on any of my stuff. I know I need to improve, but I'm not sure where to start. This is my last piece:
Hide this ad by registering as a memberJune 23rd, 2012 #2Registered User
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Not bad. If you want a critique, I'd say: use reference for the next one. It's not like there's anything massively wrong, it's just that everything's kind of slightly off.
Also, you might want to focus on the narrative here. Who is this woman? Where is she? Who is she aiming at? Right now it all feels rather generic.
As always, just my two cents.
June 23rd, 2012 #3
Also I'd think where and how you place your values, right now the lightest part of the skin values is on her butt (which also has most of the value variation) and the darkest on her armpit and her face is left flat with no value variation and the only value is kinda in the middle that calls little attention to itself. What do you want the point of interest to be? The butt or her face? (and if it's the butt then I'd rearrange the composition)
"I eat comics and poop stylization"
♞Sketchbook (Critiques, no compliments please.)
June 23rd, 2012 #4Registered User
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Thanks for the feedback! To be honest, I'm not really sure where I was going with this. I'll try to put more thought into my compositions and anatomy.


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Wages up, productivity flat
Nov 2, 2006
The news today from the Labor Department grabbed Wall Street's attention. The numbers suggest companies may need to hire more employees and pay them more. What's it mean for the economy? Jeff Tyler reports.
Living in cars
Oct 31, 2006
As rent prices continue to rise, even some fulltime workers can't afford anyplace to live — except their cars. Lisa McRee reports on one California community that's trying to help.
Youth unemployment up
Oct 30, 2006
The ILO's latest report says that 85 million young people around the globe are jobless. Hardest hit: Southeast Asia where youth unemployment has risen 85 percent over the past decade. Ruth Kirchner reports.
The income trap
Oct 27, 2006
Minimum wage is shaping up as a big economic issue in this year's midterm election. Six states have ballot measures to hike the hourly wage. Amy Scott reports.
Small business, big downside
Oct 13, 2006
Small businesses are behind the job boom in the United States, but the workforce driving it faces an unhealthy dilemma. Bob Moon reports.
When is workplace theft really stealing?
Oct 6, 2006
You take a pen or two from the supply closest. Or maybe you use the fax for private work. Do those activities count as stealing? Tess Vigeland interviews David Callahan, author of the book, "Cheating Culture."
Paycheck mistakes
Oct 6, 2006
Finders keepers, right? That's the rule. Or does it change when you receive a little extra cash . . . by mistake? Sally Herships shares her story.
The job hunt
Sep 15, 2006
A college degree can open a lot doors, but keeping them open is another story. All across the country, recent college graduates face the grueling search for work. Youth Radio's Latifah Muhammad shares her story.
Jobs for seniors
Sep 15, 2006
Older Americans want to work. So Tim Driver set up a site to match employers with eager seniors. Goodbye retirement. Hello, timesheet.
Day in the Work Life: Energy saver
Sep 8, 2006
On this week's 'A Day in the Work Life' -- our look at how folks trade their time for money -- we go green with an energy consultant.


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Trouble comes Flooding in
Sat, 05 Jan 2013 19:00
Smith handed an off-field yellow card
England flyhalf Toby Flood has been cited for an alleged tip tackle during Leicester's 19-14 win at Worcester.
Flood will face a Rugby Football Union disciplinary hearing on Tuesday, following the dangerous tackle on Worcester's Andy Goode in Friday's Premiership match.
Although Flood escaped any action for the challenge during the game, he could still be facing a suspension.
Flood has been charged contrary to Law 10.4 (j), following a report from the RFU Citing Officer Shaun Gallagher.
A ban would leave Flood in danger of missing Leicester's crucial European Cup pool games against the Ospreys and Toulouse later this month.
Flood's case will be heard by a panel chaired by Jeremy Summers.
* Meanwhile, Leicester's Matt Smith received a Level One citing for use of an elbow on Alex Grove in Friday's fixture.
Smith was charged with a transgression of Law 10.4 (a).
Smith's written warning is treated as a yellow card for the purposes of totting up in the 2012/13 season only.
|South African news
|» No need to stress about Boks
|» RIP: Full-time for Piet Malan
|» World XV call on Horrell
|» World Cup bid a four-horse race
|» SARU stand firm as Maties sue Roux


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Page 229
A systematic analysis of the information contained in reports
presented at this seminar specifies steps that seem necessary for the
development of innovation activity in the nuclear cities:
The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
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Small Innovative Business in the Nuclear Cities ."
Successes and Difficulties of Small Innovative Firms in Russian Nuclear Cities: Proceedings of a Russian-American Workshop . Washington, DC: The National Academies Press,
2002 .
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