approach to discover such inhibitors was recently reported^[@R8],[@R9]^. In this work, a cyanoacrylamide electrophile attached to a kinase-recognition scaffold was designed to form a covalent but fully reversible bond with Cys436 in the C-terminal kinase domain of RSK2. These cyanoacrylamide inhibitors provided sustained engagement of RSK2, with biochemical residence times up to 6 hours^[@R9]^. Despite these promising results, it remained unclear how residence time could be systematically modulated. Moreover, characterization of cyanoacrylamide-based kinase inhibitors has to date focused on biochemical and cellular systems, and whether such inhibitors demonstrate prolonged residence time in vivo after oral administration has not been established.

Reversible covalent drugs have at least two theoretical advantages over their irreversible counterparts. First, relative to reversible covalent drugs, drugs that rely on intrinsically irreversible chemistry (e.g., acrylamides) arethat reversible covalent BTK inhibitors exhibit varying degrees of durability, with **9** being the most durable (59% ± 17% occupancy 18 hrs post-washout, [Fig. 3c](#F3){ref-type="fig"}). Co-treatment with the protein synthesis inhibitor cycloheximide indicated that much of the apparent recovery of unoccupied BTK during the 18 hr washout period is due to BTK turnover and re-synthesis in Ramos B cells rather than compound dissociation ([Supplementary Fig. 16](#SD1){ref-type="supplementary-material"}).

BTK occupancy led to diminished signaling downstream of the B cell receptor, as revealed by a flow cytometry-based CD69 expression assay. In human whole blood, BTK inhibitors including **9** blocked CD69 expression following stimulation of the B cell receptor with anti-IgM ([Supplementary Figs. 17-18](#SD1){ref-type="supplementary-material"}). Potent BTK inhibition in cells also required Cys481 as a C481S BTK mutant transfected into HEK293 cells was \>50-fold


A trypsin stock solution (Sigma T1426) was prepared to 1 mg/ml in assay buffer. 60 μL of both the enzyme/compound mixture and the storage buffer/compound mixture were added to 120 μL of 1 mg/ml trypsin. Liquid chromatography-mass spectrometry of the samples was performed by the analytical chemistry group of the Molecular Medicine Research Institute ([www.mmrx.org](http://www.mmrx.org)). In order to calculate inhibitor reversibility, the average mass spectrometry peak area of the compound/BTK/trypsin samples was divided by the peak area for the samples containing compound/storage buffer/trypsin to get the % Reversibility.

### BTK cell occupancy using Alphascreen {#S21}

To treat Ramos B cells with compounds, 100 μL of 1 × 10^6^ cells were cultured in a 96-well round bottom polypropylene plate. 10 μL of a 1:3 dilution series of compound prepared in media10-20 × 10^6^ cells, were incubated with 1 μM PP-BODIPY for 1 hr. Protein lysates were separated on a 4-12% Bis-Tris SDS-Page gel. The BTK-associated fluorescence signal was detected by scanning the gel on a Typhoon image scanner (GE Healthcare). Total BTK was subsequently detected via Western blotting with a BTK antibody (D3H5 clone, Cell Signaling Cat\#8547) and an AlexaFluor647 anti-rabbit IgG (H+L) secondary antibody (Invitrogen, Cat\#A31573). The signal was quantified using ImageQuantTLv7.0 software. All animal procedures were performed in accordance with the Guide for the Care and Use of Laboratory Animals and had prior approval by Principia Biopharma\'s IACUC adhering to Protocol PRN-01-2011.

Alphascreen ERK phosphorylation {#S27}
-------------------------------

Human umbilical vein endothelial cells (HUVECs) were utilized to determine compound potency by measuring FGF-induced phospho-Erk1/2 phosphorylation. Approximately 30,000 cells were seeded


as often as the LCMS method would allow (approximately every 6 minutes) for about one half hour. Percent adduct for each time point was determined as described above, then plotted and analyzed using GraphPad Prism. For **9**, parent and BME adduct were not well separated on the LCMS and percent adduct was determined using the areas under the curve of the appropriate extracted mass peaks from the positive ion trace.

### Structure coordinates {#S31}

The coordinates of the BTK/**3** crystal structure are deposited in the Protein Data Bank with accession code 4YHF.

Supplementary Material {#S32}
======================

This work was supported by the US National Institutes of Health (NIH) (GM071434 to J.T., F32GM087052 to J.M.M.), the UCSF Stephen & Nancy Grand Multiple Myeloma Translational Initiative (J.T.), the Academy of Finland (V.O.P.), and the Sigridcommittee, the executive mayor remains accountable to the municipal council for all the powers and duties allocated to him. In the mayoral executive system, the mayoral committee is appointed by the executive mayor.

Geographics

The Dihlabeng Local Municipality is situated within the boundaries of the Thabo Mofutsanyana District Municipality in the Eastern Free State. The geographical area is 7550.4910 km2. The Municipality consists of the towns Bethlehem (incl. Bohlokong & Bakenpark), Clarens (incl. Kgubetswana), Fouriesburg (incl. Mashaeng), Paul Roux (incl. Fateng-Tse-Ntsho) and Rosendal (incl. Mautse).

Bethlehem is situated approximately 240km north-east of Bloemfontein, 140km east of Kroonstad and 90km west of Harrismith. The town is strategically situated in the heart of the picturesque north-eastern Free State and originally developed as a service centre. Growth is stimulated by the strategic location of


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            of the VCO 8 with each other, and then outputs to the charge pump 4 a phase difference signal indicating a phase difference (indicating the phase difference by a pulse width, for example). The charge pump 4 converts the phase difference signal into a current, and then outputs an output current. The LPF 6 smoothes the output current. The VCO 8 oscillates at an oscillation frequency according to an output voltage of the LPF 6 to output the clock. The output clock of the VCO 8 is inputted to the phase comparator 2 for feedback to the VCO 8, whereby the clock in synchronism with the input data is obtained.
FIG. 17 is a block diagram of FIG. 16. From FIG. 17, a closed loop gain of a feedback


kHz or lower, and the peaking be 0.1 dB or lower. FIG. 22 is a diagram showing PLL frequency characteristics when the loop gain is varied. When the loop gain is too small, the peaking specification cannot be satisfied, as shown in FIG. 22. When the loop gain is too large, on the other hand, the cut-off specification cannot be satisfied, as shown in FIG. 22. Accordingly, in order to satisfy the jitter transfer specification, the loop gain of the PLL circuit needs to be designed to fall between a lower limit value determined by the peaking specification and an upper limit value determined by the cut-off frequency specification.
When a VCO for operating at a high frequency is designed, however, the gain KV of the VCO is variedgreatly depending on the process, temperature, and power supply voltage. Therefore, the loop gain is varied greatly, which makes it difficult to satisfy the jitter transfer characteristic. In order to deal with this problem, Japanese Patent Application No. Hei 8-310804 discloses that the loop gain of a PLL circuit is compensated by detecting the VCO gain from a frequency converging characteristic of the PLL circuit. In this example, the VCO gain Kv is detected from a temporal change in VCO control voltage in a converging stage of the PLL circuit. The temporal change in the VCO control voltage is sampled by an A/D converter and calculated by a DSP to thereby detect and compensate the VCO gain. However, in order to detect the temporal change in the VCO


purposes of our discussion, we will limit ourselves to magazine editors.)

See, even though editors read hundreds of stories a month, they tend to see the same authors over and over, and they remember you. The first time an editor said such-and-such story was not as good as my other stories, I was over the moon. I never sold to him, but he knew my name. He found it worth remembering, and that’s huge.

If an editor is going to remember you, you want it to be for the right reasons. That means read the guidelines and follow them. You’d be surprised how many writers don’t. On the other hand, sometimes guidelines aren’t as strict as they appear. An anthology’s theme might stretch to cover your story even if itdoesn’t fit like a glove. And word limits may be flexible. If the guidelines say, “3000 – 5000 words, firm,” then respect them. But if they don’t, maybe they can be exceeded–but if you’re going to try that, ask first. You can query an editor to determine if exceptions are allowed, and the mere fact that you asked may get you the answer you want.

Well, you may get the answer you want concerning whether you can skirt the guidelines. Getting the answer you want about a sale, that’s going to take some more work. But when you sub that next story, having an editor who remembers you isn’t going to hurt…

I saw Roland Emmerich being interviewed on TV, and he said, “Films are not finished. They are just


think so. (Unfortunately, the Market agreed with me.) Still, it is a tenet of our faith (in ourselves) that one does not “self-reject.” We are poor judges of our own work. I have sent stories to markets that I thought were a bad fit, but they conformed to the market’s requirements so I sent them. And they sold. You can never tell.

Unless of course you adopt the ancient practice of never finishing because you’re afraid of the reception you’ll get. But I can tell you the reception you’ll get: Complete silence. A watched pot never boils, and an “unfinished” story never sells. Not even a pharaoh would argue with that.

To those who believe with the fiery passion of a thousand suns that “Stairway to Heaven” is the greatestwords on paper after a break feels more like the high bar of beginning a novel. I expect this will fade as I reread my last few pages and return to that world, but it’s not as easy as that. In my mind, I have that BLANK PAGE feeling.

Short stories versus novels. There are advantages to both: On the one hand there’s speed, the ability to work on several sequential projects in a shorter span; the greater likelihood of publication. On the other hand, there’s money. And recognition, from both colleagues and the reading public.

These are obvious factors, save perhaps the last. But there is no getting around that if you want to be known for your writing, you have to write novels. Unless you’re one of the


my e-reader. Sooo many choices.

I'm currently reading TOS "Serpents in the Garden" about halfway through. Really liking it so far. Also getting back into my re-read of the post-Nemesis stuff, even though I had started with the A Time to,,, series. I had read the first two books, but then got into a big star wars reading mood at the time. I'm finally back in my trek reading mood.forth by anti-union forces, will mean four years of relentless assault on the labor movement, and its further weakening. While we work on the next steps of the Sanders political revolution, which could include seizing control of the Democratic Party, we must do all we can to support economic security for workers.

Usually party platforms start gathering dust after Election Day. This time is different. The convention must be open, free-wheeling and presided over by a new, neutral Democratic National Committee chair to convey fairness.

Huge numbers of Sanders supporters felt that the often messy and chaotic primary election process blocked their desire to vote; significant changes are needed to guarantee voters, especially young people, do not feel disenfranchised. Also, we won the issues debate, and, thus, the platform needs


American." "With motorcycles on the walls." "What kind?" "Real ones." "On the walls?" "Yeah, I thought you'd like that." "Fuck the motorcycles, the food is what counts!" "Get in the car!" "What's going on here?" "THE BONE MAN" "Wait here!" "You have the keys?" "No." "Hand them over!" "Please, moneywas tight." "I'll pay somehow..." "Be reasonable, please!" "No!" "You should have paid on time!" "I know, but I need the car, please." "Sorry." "You got 3 reminders, right?" "I'm a single mom, We need to get to kindergarten." "Please." "Talk to the leasing company!" "No." "Please, step aside!" "Let me out on the other side ofthe bridge." "A small beer!" "Hi, Brenner." "Done." "Thanks." "This is Isabel!" "Hello." "Hi!" "We met last night at the Skybar." "Cheers." "Haveright." "Maybe I'll go away." "Go where?" "Anywhere." "Start over." "Fresh start." "What would you do?" "Work in a restaurant." "It's all I know how to do." "Jerk." "My body feels like rubber." "Rubber would be cool." "Ifyou're made of rubber, and you fall down, you automatically bounce back up." "Say that again." "Ifyou're made of rubber and you fall, you bounce back up," "like a ball." "Why?" "Forget it." "What are you waiting for?" "." "What do you mean "waiting"?" "Just in general." "What should I be waiting for?" "I don't expect much anymore." "I wish I could take you home." "I've heard that before." "But nobody does it." "Well, I'm serious." "Just say the word." "I better not." "But you want to leave." "Not to go


"He's throwing more clothes away than I own!" "Why don't you tell me what's going on?" "Mr. Horvath is working on an important exhibition... and doesn't want to be disturbed." "And you happen to know that?" "I'm his sister." "He saw the suitcases." "Then hide them." "Why?" "Horvath won't be needing them." "Sometimes I get so scared." "We'll get through this." "You're still here." "I thought you were done here." "I decided to extend." "Because ofthe fresh air?" "." "Yeah." "And the friendly people." "Here, I'll help you." "Aren't you bored in the country?" "No, todaywas fascinating." "I sawyour machine." "My machine?" "ln the basement." "Who showed it to you?" "Your daughter-in-law." "Room number?" "Seventeen." "See, that's how it is in the country." "What?" "You meet the wholewhore can visit once a month." "I still have money, Pauli." "I want the family business." "You're not cut out for it." "People don't like you." "You arrogant old bastard." "You wanted it this way." "C'mon, be smart." "Take the money." "Open up!" "You won't tell me what to do ever again!" "Hello." "I want to fille a report." "That's our parking space." "My father killed a man." "That's still our parking space." "But..." "Pauli, get off our parking space, alright?" "Anything else?" "Yes." "Take the bones downstairs." "Brenner." "I'm disappointed in you." "What's gotten into you?" "You weren't such an asshole before." "I'm coming to pick up the car myself." "Kick him out!" "He's not on the payroll." "And this goes with that." "We don't investigate movie


Matrix effects in analysis of β-agonists with LC-MS/MS: influence of analyte concentration, sample source, and SPE type.
The synergistic influences of analyte concentration, sample source, and solid-phase extraction (SPE) type on matrix effects in the multiresidue analyses of eight β-agonists with LC-ESI-MS/MS were evaluated. Porcine muscle and liver extracts and urine from diverse sources were purified by strong or mixed-mode cation exchange and molecularly imprinted polymer SPE cartridges, respectively. Three spiked concentrations (2, 10, and 20 ng/mL) of eight β-agonists in the purified matrices and the different sample sources were analyzed. The results show that for most β-agonists there are significant differences in matrix effects between analyte concentrations or sample sources (P < 0.05), whereas there is no significant difference in matrix effects between different SPE cartridges (P >exponentially raises the sales price, seriously inhibiting the spread of a large-size coordinate input apparatus and an application using it.
In the light shielding coordinate input apparatus shown in FIG. 16, the sensor units 2, arithmetic control circuit 3, and retroreflecting member 4 are main components and attached to the screen board. Even if the apparatus becomes large, the arrangement of the main components remains unchanged, and the cost of the material of the screen board occupies most part of the cost rise caused by upsizing.
A user interface operated by touching the display screen of a display apparatus is intuitive and usable by everyone and has gone mainstream in mobile devices now. Such an operation is requested of even an apparatus having a larger display screen.
Detailed applications of a


a touch operation, the arithmetic control circuit 3, and the retroreflecting member 4. If these main building components can be attached to, for example, a whiteboard at predetermined positions and sizes, a touch position on the whiteboard can be detected. Using an existing whiteboard as the screen board can omit, from indispensable building components, the screen board itself which occupies most of the cost. This can greatly suppress the product price and provide a touch operation environment at low cost even for a large screen.
The position detection principle of the light shielding coordinate input apparatus geometrically calculates a touch position based on light shielding directions (=angles) of the touch position output from at least two sensor units, and distance information between these sensor units. To detect a touchmix, strong 6'3", 195-pound frame, and a deceptive delivery, he's been a nightmare for minor league hitters. In 12 starts at High-A Lake Elsinore, he's pitched to a 1.21 ERA and 0.69 WHIP while holding opposing hitters to an absurd .137 batting average and racking up 83 strikeouts in 59.2 innings. The 20-year-old is ready for the next challenge.

3. OF Jo Adell, Los Angeles Angels (AA)

After dealing with ankle and hamstring injuries during spring training, Adell is back to 100 percent and has gotten right to work making up for lost time. The 20-year-old is hitting .328/.400/.582 with eight doubles, three home runs and 12 RBI in 18 games between High-A and Double-A. He's a true five-tool standout and a potential superstar in the making who could join


previous aggravated felony conviction. On the same

day that Nava-Hernandez was indicted for violating § 1326, the United States

filed a Notice of Sentencing Enhancement (the “Notice”). The Notice advised

Nava-Hernandez that he was subject to the enhanced penalties set out in §

1326(b) based on a prior aggravated felony conviction. In a written statement

made in advance of his guilty plea, Nava-Hernandez acknowledged that the

maximum term of imprisonment he was facing was twenty years. Furthermore, in

calculating the appropriate sentence, the Presentence Report increased Nava-

Hernandez’s offense level by sixteen points pursuant to United States Sentencing

Guideline § 2L1.2(b)(1)(A) based on his prior aggravated felony. Nava-

Hernandez did not lodge any objections to the Presentence Report. The district

court ultimately sentenced Nava-Hernandez to a term of imprisonment of seventy

months.

      On appeal, Nava-Hernandezin this region as a chiral partner of Nambu-Goldstone boson $\pi$. Its mass value is predicted to be twice of constituent mass of a $n$ quark in the extended Nambu-Jona Lasinio model[@rf:5] as the low energy effective theory of QCD. It is vitally important to observe the sigma in production processes as well as in the scattering process.

=6. cm

The GAMS group has observed huge $\pi^0\pi^0$ events below 1 GeV/c$^2$ in a proton proton central collision process at 450 GeV/c. Details of the experimental condition and data are described in reference [@rf:6]. It shows a resonant peak at 500-600 MeV/c$^2$, as shown in Fig.\[fig:1\](a). It can be described by a $S$-wave Breit-Wigner interfering with $f_0$(980). The variant mass and width method(VMW)[@rf:10] is applied to the mass spectrum. Here we


                   ("s", ERR_error_string( ERR_get_error(), nullptr) ) );
    }
    EVP_CIPHER_CTX_set_padding( my->ctx, 0 );
}
aes_decoder::~aes_decoder()
{
}

uint32_t aes_decoder::decode( const char* ciphertxt, uint32_t ciphertxt_len, char* plaintext )
{
    int plaintext_len = 0;
    /* Provide the message to be decrypted, and obtain the decrypted output.
    *    * EVP_DecryptUpdate can be called multiple times if necessary
    *       */
	if (1 != EVP_DecryptUpdate(my->ctx, (unsigned char*)plaintext, &plaintext_len, (const unsigned char*)ciphertxt, ciphertxt_len))
    {
        FC_THROW_EXCEPTION( aes_exception, "error during aes 256 cbc decryption update",
                          ("s", ERR_error_string( ERR_get_error(), nullptr) ) );
    }
    FC_ASSERT( ciphertxt_len == static_cast<unsigned>(plaintext_len), "", ("ciphertxt_len",ciphertxt_len)("plaintext_len",plaintext_len) );
	return plaintext_len;
}
#if 0
uint32_t aes_decoder::final_decode( char* plaintext )
{
    return 0;
    int ciphertext_len = 0;
    /* Finalise the encryption. Further ciphertext bytes may be written at
    *    * this stage.
    *       */
    if(1 != EVP_DecryptFinal_ex(my->ctx, (unsigned char*)plaintext, &ciphertext_len))
    {
        FC_THROW_EXCEPTION( exception, "error during aes 256 cbc encryption final",


 *       */
    if(1 != EVP_DecryptUpdate(ctx, plaintext, &len, ciphertext, ciphertext_len))
    {
        FC_THROW_EXCEPTION( aes_exception, "error during aes 256 cbc decrypt update",
                           ("s", ERR_error_string( ERR_get_error(), nullptr) ) );
    }

    plaintext_len = len;

    /* Finalise the decryption. Further plaintext bytes may be written at
    *    * this stage.
    *       */
    if(1 != EVP_DecryptFinal_ex(ctx, plaintext + len, &len))
  on what you want your prospects to do!

Prospecting on Social Media is more than just slapping your company link or the link to your product. It needs to speak to who you are as an Entrepreneur and as a person. Be creative, be interesting, and let your personality start to come out. There are a ton of EssentialSocial Media prospecting tools and programs that will help you with this.

When you let your personality come out in your Social Media posts, people will begin to like you… trust you… and know you. That is what is going to put money in your pocket.

I shot a video that talks more about how to Get Prospects To See Your Social Media Posts, and How To Use Social Media For Business. Check


should always be on the lookout for new information so your Network Marketing can grow into a great business. In order to succeed, you should spend a significant amount of time reading books about Social Media, Network Marketing, and other outlets to start getting Network Marketing leads online. You can learn a lot from webinars conducted by successful Network Marketers who are from your company or from other organizations. The more you know about Network Marketing, the more helpful you will be to yourself and others.

People can't resist a bargain! Look for a company in Network Marketing that gives you coupons to distribute to your customers online. Give coupons to your best customers or organize competitions or drawings on your Facebook Business page to gain attention to youforever, then you need to have some scientific basis for making that claim – not to mention a great deal of research cited. If customers find out you aren’t telling them the truth about one thing, they won’t trust anything you say.

6. Contact information: Customers do not trust businesses that do not have contact information listed. It's not enough to have just an email or contact form. You need to have at least a phone number and social media profile(s) listed on your website at the very minimum.

If you follow this Vital Landing Page Checklist To Grow Your Internet Business, you will attract and develop a large customer base for your business.


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Tell the community what you thought about it by posting your comments here!low concentration (*e.g*., 20 μmol/L) with viabilities of 58.08±8.32%, 50.65±10.91% and 63.26±6.50% at 12.5 μmol/L, respectively. However, when the drug concentrations were increased to more than 20 μmol/L, the anticancer effects of the medications showed great differences ([Fig. 2](#f0010){ref-type="fig"}A). For example, when the drug concentrations were 25 μmol/L, curcumin liposomes had a low A549 cell viability of 13.50±1.79%; but free curcumin and gemcitabine only lowered cell viabilities to 38.48±6.34% and 47.80±8.57%, respectively. Furthermore, when the drug concentrations were up to 50 μmol/L, the cell viabilities were 26.86±2.58%, 6.28±0.62% and 38.82±15.83% for free curcumin, curcumin liposomes and gemcitabine, respectively ([Fig. 2](#f0010){ref-type="fig"}B). Therefore, curcumin shows high *in vitro* anti-lung cancer cell effect, even better than the clinical first-line anticancer drug, gemcitabine. Other reports also show the high anticancer effect of curcumin[@bib32], [@bib33].


day. Now after following Leanne’s advice and using her recipes, I’ve finally started to have mental clarity and energy, with ZERO cups of coffee.

I love this program! After watching some of Leanne’s videos, I decided to take a risk by eating high-fat. My body has healed SO MUCH over the past few months. Fat fueled is an awesome guide to eating high fat and healing your body.

 Luise

I’ve been devouring your No Sugarcoating podcast; I love you and Amber. I’m about halfway through the Fat Fueled Audiobook. I truly appreciate Leanne’s positive, “listen to your body” message. Please keep doing what you are doing. I am feeling so much better eating this way.

 Winni

I have had issues with my menstrual cycle and being on oral contraceptives. I sawThe candidate will also gain critical experience in clinical assessments necessary for successfully working with children with ASD. In addition, the candidate will undertake formal coursework and attend seminars in functional neuroimaging, clinical psychology, and computer programming to achieve this goal. The research project proposed by the candidate will enable the acquisition of the skills required to become a successful independent investigator in the field of developmental cognitive neuroscience. ASD is a complex neurodevelopmental disorder of largely unknown etiology, characterized by social communicative impairments, restricted interests, and repetitive and stereotyped behaviors. The main goal of the proposed research is to examine aberrant structural and functional brain connectivity underlying atypical cognition and behavior in children with ASD. The candidate proposes to probe large-scale brain networks using DTI and fMRI


In a context of peripheral node of the motorway, the building is set within a park, planted with native species, in which a sort of town square accompanied to the entrance. The dynamism of the client is shown in architecture, volume changing, a prism completely covered in black glass faceted and integrated photovoltaic panels.

In plan the building is on the east-west, in two wings separated by a central block of facilities (stairs, toilets and bars). Operating areas are designed as open-space, while the executive offices, the private sector, are tested in the east of the building, projected to the outside and suspended in a vacuum.

The entire structure is of type point with beams and reinforced concrete pillars brick and cladding. Building components and systems provide the Class A24 h (up to 100 x 10(9)/litre) with great variability in subsequent measurements. Neutrophilia over 90 per cent and pH under 6.9 were the most consistent findings in the infected synovia. Increased total protein was also significant and was progressive throughout the experiment. Serum and synovial glucose difference and synovial lactate had more diagnostic value in the acute stages than in the chronic stages. The control joints elicited an inflammatory response manifested by increased leucocyte count, moderate neutrophilia, slightly increased total protein concentration, and slightly decreased pH, but all reactions were minor in comparison to those in the infected joints.


a hydrogen bond between the A-propionate of the haem to Ser126 OH. As a result, two water molecules are hosted at the entrance of the proximal site (hydrogen bonded to Ser126 OG and to Gln130 NE2, respectively), and four additional water molecules and one acetate ion fall next to the propionate ([Supplementary Fig. 3a](#S1){ref-type="supplementary-material"}). This exposure to a polar aqueous environment would favour oxidation of the ferrous haem, which is consistent with the low GLB-12 redox potential reported. On the distal site of the haem cavity, the D-propionate stabilizes the location of the E-helix N-terminal region through hydrogen bonding ([Supplementary Fig. 3a](#S1){ref-type="supplementary-material"}). In addition, residues Phe89 and Phe96 (surrounding the distal His92) are part of a wide cluster of aromatic/hydrophobic residues (Val54, Phe58, Leu59, Val62, Phe73, Phe152) (notpresent following both control and *glb-12* RNAi ([Fig. 6b](#f6){ref-type="fig"}). An increase in germ cell corpses can be caused by an increase in germline apoptosis, or by a decrease in corpse engulfment and removal by the somatic gonad. Because *glb-12* RNAi still caused increased germline apoptosis in engulfment-defective mutants, did not affect the speed of corpse removal by the somatic gonad and had no visible effects on somatic gonad structure ([Supplementary Fig. 6a--c](#S1){ref-type="supplementary-material"}), we concluded that GLB-12 is directly involved in germline apoptosis. In loss-of-function mutants for the pro-apoptotic genes *cep-1*, *ced-13* and *egl-1*, GLB-12 depletion still caused an increase in germline apoptosis ([Fig. 6b](#f6){ref-type="fig"}; [Supplementary Fig. 6d](#S1){ref-type="supplementary-material"}), indicating that GLB-12 does not signal through these proteins. The p38/JNK MAPK pathways act independently of CEP-1, CED-13 and EGL-1 ([Fig.


while plasma membranes form a physical barrier to ROS, ROS transport across membranes could occur via selective membrane channels. This has been observed for both O~2~^.−^ and H~2~O~2~ with certain classes of anion channels[@b29] and aquaporins[@b4][@b40][@b41][@b42]. This ROS transport across membranes has therefore been hypothesized to participate in the regulation of redox signalling and could also be involved in GLB-12-mediated signalling. Overall, our results show that redox signalling by GLB-12 is regulated by multiple control layers. Interesting to note is that NADPH oxidase, a known ROS generator, also displays a very specific subcellular localization that is related to its function, and also appears to interact with SOD enzymes[@b26][@b43]. These shared characteristics between GLB-12 and NADPH oxidases indicate that redox signalling proteins function according to similar principles. Furthermore, thewere set to 'not a number\' (NaN). Relative H~2~O~2~ levels in these processed images were quantified by (1) selecting a polygonal region, which showed the probe within the somatic gonad and which showed no interfering background fluorescence from the gut, (2) calculating the average pixel intensities within this region for both the 405 nm and the 488 nm image and (3) calculating the ratio of the 405 nm average pixel intensity over the 488 nm average pixel intensity.

Recombinant expression of GLB-12
--------------------------------

To express recombinant GLB-12, young adult worms were collected and total RNA was prepared using the TriZol method (Invitrogen) followed by LiCl precipitation (Ambion). cDNA was prepared using the OneStep RT-PCR kit (Qiagen). Cycling conditions were as followed: 30 min at 50 °C for the RT reaction, followed by 15 min at 95 °C for the


on this, and the interaction of GLB-12 with CCP. Except for the pH depence, these measurements were repeated using dissolved protein samples and showed highly comparable results. All other measurements were performed on dissolved protein samples. All measurements were carried out under nitrogen atmosphere at room temperature (22±2 °C).

Real-time quantitative RT-PCR
-----------------------------

Total RNA was isolated from harvested *C. elegans* worms using the RNeasy Midi Kit from Qiagen (Hilden, Germany), according to the manufacturer\'s instructions. A DNase I (Zymo Research, Orange, California) digestion step was subsequently performed to remove genomic DNA. First strand cDNA was synthesized using an oligo(dT) primer and a Moloney murine leukemia virus reverse transcriptase (Fermentas, Vilnius, Lithuania).

Quantitative RT-PCR was carried out using a Rotor-Gene 2000 centrifugal real-time cycler (Corbett Research, Mortlake, Australia) using the Platinum SYBR GreenqPCR SuperMix-UDG (Invitrogen). Each reaction contained: 12.5 μl of the Platinum SYBR Green qPCR SuperMix-UDG, 200 nM of forward and reverse primers and 5 μl cDNA (1:40 RNA dilution), to a final volume of 25 μl. Amplification was performed in 0.1 ml real-time PCR tubes (Corbett Research) placed in the 72-well rotor of the Rotor-Gene instrument. The cycling conditions were as follows: 50 °C for 2 min, initial denaturation at 95 °C for 2 min, followed by 45 cycles of 15 s at 95 °C, 30 s at 60 °C and 30 s at 72 °C (gain set at 8 for SYBR Green). Following the final cycle, melting curve analysis was performed to examine the PCR specificity in each reaction tube (absence of primer dimers and other nonspecific products). All PCR reactions were performed in triplicate. *Ct* values were transformed to relative quantities


and were normalized using the geometric mean of three reference genes[@b56]. Four biological replicates were carried out for each experiment. Primer sequences can be found in [Supplementary Table 2](#S1){ref-type="supplementary-material"}.

Crystallization and structure determination
-------------------------------------------

Atomic coordinates and structure factors determined from the GLB-12 crystal have been deposited in the Protein Data Bank, with entry code 4bja. Crystals of GLB-12 were grown at 4 °C by the hanging-drop vapour diffusion method, by mixing 1 μl protein solution with 1 μl crystallization well solution containing 2 M (NH~4~)~2~SO~4~, 0.2 M Na-acetate, 0.1 M Na-acetate pH 4.6. Crystals usually grew in about two months, and were cryo-protected with the same crystallization well solution supplemented with 30% glycerol, prior to cryo-cooling in liquid nitrogen. The crystals belong to the space group *P*6~5~22, with unit cell parameters *a*=50.4 Å, *b*=50.4 Å, *c*=245.3 Å, γ=120°, andthe last time I realized anything about it was 15 years ago.Looking at today's front page, seeing that the number-three headline is, if you can fathom this, "Democrats win in New Jersey, Virginia, California," it's dawned on me that The Post not only wants to live in a one-party KMT state -- that much is obvious -- but it actually thinks it still lives in a one-party state. Don't follow my reasoning?

Well, what I mean is that The Post's news judgement, if you dare to call it that, is that minor US elections constitute the third-most important thing they could possibly inform their readers of today. And this might have been true back when US soldiers made up a big fraction of The Post's readers. But today? Perhaps


and Taiwan has more international leeway. Sure, Wang may never have had a chance to represent Chen, but if you don’t try to advance your position, you certainly won’t get anywhere. I hope that when Ma is elected president, he won’t take such a spineless approach as he seems to be advocating now.

A gesture of goodwill indeed. Panda spies, I say! According to this article, a nine-person team has whittled down the field of eligible pandas to 11. They plan to match the pandas to their destination based on “physiology, psychology, behavior, appearance, genetics and age.” Right. It’s clear to me they’re choosing pandas that are likely to make good operatives. Note that a couple of the males are described as having big mouths. Fat chance they’ll becares if the tax structure is leaky and the national debt is approaching legal limits -- roads to nowhere must be built! Artificial lakes must be constructed! Cable cars must run to the tops of the highest mountains!

You'll note that useless roads, destructive lakes, and moronic cable cars are all projects that create adverse environmental consequences. Now, I don't suspect the government of fouling the environment just for the fun of it, but they sure don't let nature stand in their way as they rush to spend public money on construction projects that make their cronies fat and happy.

Well, I've got an idea. Why doesn't the government, since it's so eager to divert taxpayers' money to contractors, finally invest in sewage treatment for every household, every place of


business, every public facility on the entire island?

I don't have the figures in front of me, but Taiwan's sewage connection rate comes in at something like 30%. Surely, surely, correcting that national disgrace would cost just as much money as do these idiotic roads that create landslides, artificial lakes that only destroy habitat, and cable cars that would allow ramshackle Disneylands to be built on top of Yushan.

Fixing the sewage problem once and for all seems like a win-win situation. It would produce great public benefit while running through enough money to satisfy even the most corrupt member of the Legislative Yuan. The opportunity for kickbacks would be vast. The rivers would be so much cleaner.

If it's shameful that we have bloated corpses on New Orleans streets, it'seven more disgraceful that the infant mortality rate in America's capital is twice as high as in China's capital. That's right - the number of babies who died before their first birthdays amounted to 11.5 per thousand live births in 2002 in Washington, compared with 4.6 in Beijing.

While I share Kristof's outrage at the Bush Administration's disgraceful response to the disaster in New Orleans and his concern about the poor in America, I wonder about this figure. I suspect that when health authorities in Beijing calculate infant mortality rates, they are looking at infants born to registered residents of Beijing. I believe there are something like 3 million migrant workers in Beijing whose childern are not counted. Since these workers basically have no access to health care, the


of the DPP as this one.

Monday, August 29, 2005

Tough times in Qingquan

This weekend, a few friends and I made an overnight trip to the mountains of Hsinchu. We all had a fine time up at altitude -- barbecuing under an overhang in the rain, walking the riverside paths at night. But not all of it was fun and games, because we couldn't help observing that the people of Qingquan and vicinity are suffering from some very serious social problems.

It's not news to anyone that Aboriginal communities often have big trouble adapting to their changed worlds. But for me... well, certain truths don't become real in my mind until confirmed by detail. In this case, pathetic detail.

On Sunday morning, my friend and I walked to the store to buya Guatemalan airplane in Taiwanese airspace, please e-mail me. Can you picture the trade representatives from the two governments wasting their time hammering this out?

Here is an article about a lotto winner who gave NT$20 million to a charity that cares for "comatose people from low-income families." I just didn't know such a charity existed. [This story is actually from a few weeks ago. Today we learn that another lotto winner has given NT$50 million to charity, but I'm not linking to that story because the guy picked dull charities.]

And from this story we learn that "a leading plastic surgeon and his colleagues in the southern port city of Kaohsiung will offer their services to 100 fathers who wish to have wrinkles and age marks removed to give


time there anyway.

: So you didn’t get a hotel. You have other options that aren’t the Hall H line, we promise. Although downtown hotels basically want attendees’ first born in exchange for a room (the Hilton Bayfront has rooms starting at just $899 a night, kids!), with a quick search we were able to find several motels in San Diego for under $200 a night. You won’t be spending much time there anyway. Accept Your Fate: If all else fails, if you at least have somewhere to stay — make the most of it. So maybe you’re in Mission Valley instead of the Gaslamp District. There are plenty of Comic-Con shuttles that run 24 hours, or you can even look into renting a car and buying parking. Youwas no doubt a journalistic coup for Jarecki, co-writer Marc Smerling, and HBO. Durst was arrested Saturday in New Orleans in connection with Berman’s death—although it’s still unclear whether that came as a result of the program. But soon after its bombshell conclusion on Sunday night, questions arose regarding the final episode’s timeline, as well as filmmakers’ cooperation with police since unearthing new evidence. The finale appears to have misled viewers about the chronology of events, namely flipping the order of Durst’s interview with Jarecki and his 2013 arrest for violating his brother’s restraining order. Jarecki and Smerling dodged the question in an interview with The New York Times on Monday, and they’ve since canceled other media appearances and released a statement denying interview requests.

The confusion doesn’t nullify


the rest of Jarecki & Co.’s investigation, but it does resurrect familiar questions for the genre. Documentarians don’t boast the same flexibility as writers–they generally need audio or video recordings of events in order to advance stories–and real-life chronology is easily sacrificed for theatrical effect. The issue emerging from The Jinx is where journalism ends and entertainment begins. That line has grown increasingly blurry in recent years, and the massive success of HBO’s series and its true-crime counterpart, Serial, suggest the trend could continue.

Both of the narrative-driven works take on a cinematic form, enticing their audiences to return with the implicit promise that more damning evidence would be unearthed in subsequent episodes. They also allowed viewers to peak behind the curtain. If Serial taught us anything–and The Jinxin the cases we investigated were also members of the innovation network of the other interventions ([Fig 2](#pone.0197993.g002){ref-type="fig"}).

### Network-based stakeholder typology, scaling out, and scaling up {#sec009}

The innovation system literature commonly describes the dissemination of the use of innovations among different stakeholder groups as *scaling out*, whereby innovations developed by livelihood interventions are used in another geographical location \[[@pone.0197993.ref018], [@pone.0197993.ref019]\], or *scaling up* whereby innovations are institutionalized and are commonly used at different geographical locations and in different institutional setups \[[@pone.0197993.ref020]--[@pone.0197993.ref023]\].

Both definitions are based on geographical location, and scaling up also includes an element of institutional embedding. Spreading the use of innovations from MSPs to outside ([Fig 2](#pone.0197993.g002){ref-type="fig"}) implies a change in functional stakeholder types, such as from researchers to policymakers, and mostly entails institutional embedding. Therefore, such


[@pone.0197993.ref050]\]) insignificant country variation implies that the role of the institutional environment was reflected through other significant factors in our models: initial innovation network characteristics, funding provided, and type of activities targeted by MSPs ([Table 6](#pone.0197993.t006){ref-type="table"}). Of these factors, decisions on funding and type of activities targeted by MSPs are less likely to be influenced by the specifics of the institutional environment, as in our three cases the managing organization had the dominant role in making funding and activity decisions. Thus, in our cases, initial innovation network characteristics have a high chance of sufficiently representing the effects of the institutional environment on changes triggered by MSPs.

Our data show that the likelihood of staying in all three networks increased if the organization received direct funding. Moreover, the likelihood ofJoin Senator Gallivan’s efforts to protect your tax dollars!

Yes Senator, I agree with you that public assistance should not be used to purchase items such as alcohol, lottery tickets and cigarettes, and by signing this petition I encourage the State Assembly to pass the Public Assistance Integrity Act.


reactions including dehydrogenases, reductases and monooxygenases were considered for tailor-made designer cells \[[@CR36]--[@CR39]\], recently also TA-catalyzed reductive amination attracted attention to being included in artificial in vivo pathway construction \[[@CR40], [@CR41]\]. In this context especially the amino functionalization of alcohols by combining an alcohol dehydrogenase (ADH) with a TA in a redox self-sufficient fashion has been extensively studied \[[@CR42], [@CR43]\]. Moreover, transamination was investigated with recombinant yeast single-cells of *Saccharomyces cerevisiae*, exploiting cell metabolism for cofactor regeneration \[[@CR44], [@CR45]\]. To our knowledge however, there are no reports on transferring the classic TA-catalyzed reductive amination machinery into a single recombinant *E. coli* cell. Therefore, in the present study the orthogonal cascade was translated from an in vitro to an in vivo mediated approach by generating all required enzymes withinthey provided. The genes encoding NADH-recycling enzymes were cloned into pBAD28 (plasmid 2) under control of the arabinose-inducible the P*BAD* promoter \[[@CR48]\] and ribosome binding sites upstream of each gene. Due to a different origin of replication (p15Aori) and a chloramphenicol resistance, pBAD28 provides the appropriate features to be compatible with pTrc99A (pBR322ori, *bla*). However, since it also contains the same β-lactamase gene, we removed parts of it in order to inactivate the ampicillin resistance (pBAD28∆*bla*). The newly obtained plasmids were designated pBAD28∆*bla*-*fdh*, pBAD28∆*bla*-*gdh*, pBAD28∆*bla*-*ptdh*.Fig. 1Tailored construction of single-cell catalysts for asymmetric amination using a module-based catalyst design. Module I provides various enzymes catalyzing reductive amination of the target substrate, module II offers two enzymatic options for amine donor regeneration and finally, nicotinamide cofactor recycling is performed by components


PLP) with [l]{.smallcaps}-alanine as amine donor and a substrate concentration of 25 mM. The particular co-substrate was applied according to the used cofactor-recycling enzyme. Together with the FDH catalyzed recycling system ammonium formate was used, while for the GDH system glucose and for the PtDH system sodium phosphite was required. For the GDH and the PtDH system additionally ammonium acetate was needed as nitrogen donor. The recombinant *E. coli* catalyst was employed either in form of resting cells (50 mg resuspended in 500 µL reaction buffer) or as cell-free extract (\~350 µL, corresponding to 50 mg wet cells mixed with 150 µL reaction buffer) in an Eppendorf tube (1.5 mL). Alternatively, lyophilized single-cells (corresponding to 50 mg wet cells) or lyophilized cell-free extract (corresponding to 350 µL lysate) were rehydrated in reaction buffer for 15 min at 30 °Cmy insecurities get the best of me. If the sponge has been squeezed to the last drop, that just means it's time to go back to the well.

What well? Take your pick. They're all around you! Every facet of your life can be a wellspring of creativity if you look from the right angles. What's been on your mind lately? What problems are you tangling with? Does your job have you down? Have there been any wild developments in one of your personal relationships? If it's compelling enough to hold your attention, or better yet, steal your attention when you're trying to focus on something else, chances are it can become story fodder. It might even be a little therapeutic.

If that still doesn't work, then turn your gaze


media containing collagen type I, heparin-carrying polystyrene, and fibroblast growth factor (FGF)-2. These expanded mouse ATSCs maintained their multilineage potential for differentiation into adipocytes, osteoblasts, and chondrocytes. Therefore, this method, which uses autologous cells and low serum media, may be able to be utilized for clinical cell therapies.prime factors of 48048304.
2, 757, 3967
What are the prime factors of 3160475463?
3, 1053491821
List the prime factors of 1887309112.
2, 13, 83, 218641
List the prime factors of 23087745.
3, 5, 23, 22307
What are the prime factors of 44488921?
44488921
List the prime factors of 45242848.
2, 7, 17, 109
List the prime factors of 42969527.
1229, 34963
What are the prime factors of 32790702?
2, 3, 7, 111533
List the prime factors of 253767895.
5, 19, 2671241
List the prime factors of 10330334.
2, 7, 859
What are the prime factors of 171566917?
10331, 16607
What are the prime factors of 227832924?
2, 3, 11, 163, 10589
List the prime factors of 32596333.
7, 11, 47, 9007
List the prime factors of 338641172.
2, 84660293
What are the prime factors of 52450759?
179, 293021
What are the prime factors of 401773394?
2, 11, 18262427
List the prime factors of 1263383207.
19, 31, 53, 40471
What are the


are the prime factors of 192666078?
2, 3, 11, 23, 42307
What are the prime factors of 92232508?
2, 53, 435059
List the prime factors of 86041686.
2, 3, 14340281
What are the prime factors of 54908040?
2, 3, 5, 11, 41597
What are the prime factors of 1554281615?
5, 617, 503819
What are the prime factors of 339187417?
17, 23, 867487
What are the prime factors of 2913485792?
2, 7, 97, 134089
List the prime factors of 50432523.
3, 17, 58169
List the prime factors of 347270110.
2, 5, 11, 3157001
What are the prime factors of 8803081?
7, 631, 1993
What are the prime factors of 487154468?
2, 1129, 107873
What are the prime factors of 240702858?
2, 3, 11, 173, 7027
List the prime factors of 21976150.
2, 5, 7, 37, 1697
List the prime factors of 47488445.
5, 23, 412943
What are the prime factors of 292936265?
5, 17, 163, 21143
List the primeit out in the first place." "It wouldn't have been worth it to spend 15 years of my life composing a sonnet for someone to be able to grasp its meaning in 15 minutes." "Surely, you're not like Molière, a writer for his maid." "What do you mean?" "If I wrote for my cook, I wouldn't write differently." "But after all, obscurity is not without danger." "It's equally dangerous whether it stems from the insufficiency of a reader or that of a poet." "But evading this work is trickery." "If a person of average intelligence and of insufficient literary preparation accidentally opens a book written in this manner and pretends to enjoy it, they are misunderstood." "Everything should have its place." "There should always be a mystery in


won't be gathered in some ashes' amphora" "On a table, in the empty room:" "here is no ptyx," "Abolished bauble of sonorous uselessness," "(Since the Master's gone to draw tears from the Styx" "With that sole object, vanity of Nothingness)." "But near the casement wide to the north," "A gold is dying, in accord with the décor" "Perhaps, those unicorns dashing fire at a nixie," "She who, naked and dead in the mirror, yet" "In the oblivion enclosed by the frame, is fixed" "As soon by scintillations as the septet." "It's not exactly plastic, I admit, but at least it is as "black-and-white" as possible," "and it seems to me to be ready for an eau-forte of Dream and Emptiness." "For example, an opened window at night, twowas quantile normalized using the R Limma package [@pone.0055895-Smyth1]. To maximise integration of data, spanning different resources and from different sources (e.g. expression arrays, gene ontology annotations, gene lists etc), all genes across all used resources were re-annotated to HUGO Gene Nomenclature Committee (HGNC) approved symbols. The complete HGNC list was downloaded (on 2012.08.16). Each gene was re-annotated to the latest approved symbol if an unambiguous mapping (i.e. single symbol mapping to an approved symbol) could be determined, else the original gene name was maintained.

DLBCL Classifier Generation: Data Preparation {#s2c}
---------------------------------------------

For all data sets the probes for each of the classifier genes were merged using 2 methods: (1) the median value across the probes for each gene (**MedianMerge**), and (2) the approach used by Monti et al. - taking


trained Weka classifiers output predictions for each sample analyzed consisting of p-values for each of the 3 classes, the class with the largest p-value giving the predicted class. The LPS classifiers assign everything with a confidence greater than a p-value threshold (0.8/0.9) to ABC/GCB and everything below the threshold to Type-III/Unclassified. The predicted classes were used to rank the classifiers (see Classifier Ranking).

The 6 best individual Weka classifiers (LMT, SMO, BayesNet, J48, RF100, RF200) were combined using the Weka Vote scheme with the average of probabilities combination rule. Each classifier was removed in turn to generate all possible 5-tool classifiers (5N). This process was iterated with the best meta-classifier at each N progressing to the next level (e.g. best 5N → all possible 4N). As with the individualnumber again had no beneficial impact on survival separation for either LMT_J48_RF100_SMO or LPS classifiers ([Table 4A](#pone-0055895-t004){ref-type="table"}). Training data set had limited impact on the performance of the classifier in evaluating GSE4475, giving p-values of 0.004 or 0.003 whether trained on Wright or GSE10846 R-CHOP data, both outperforming the significance of survival separation gained using the published classes for this data set (p-value 0.0108).

10.1371/journal.pone.0055895.t004

###### Effect of data set and classifier gene number on survival.

![](pone.0055895.t004){#pone-0055895-t004-4}

  A


FDR \<0.01, **\*** FDR \<0.0.

10.1371/journal.pone.0055895.t007

###### Selected gene signatures significantly enriched or depleted in the GCB meta-profile.

![](pone.0055895.t007){#pone-0055895-t007-7}

  Enriched                                                                                and provide evidence for the particular significance of chr3 and chr18 deregulation in ABC-DLBCL.

![Chromosome cytoband enrichment/depletion in the ABC class.\
Human chromosomal cytobands are depicted using gray scales, with chromosomes displayed vertically in numerical order. Enrichment or depletion of cytobands was assessed using a hypergeometric test and the MSigDB C1 component against the meta-profiles and across differentially expressed genes for each data set individually. Observed enrichments and depletions are shown as the average Z-scores with red to blue color scale (average Z-score = +6 to −2) as indicated in the insert. These are derived from analyses of individual data sets ([Table S9](#pone.0055895.s010){ref-type="supplementary-material"}), with significant enrichment in \>5/11 data sets used as threshold for inclusion. Regions additionally identified as significantly enriched in the ABC meta-profile ([Table S8](#pone.0055895.s009){ref-type="supplementary-material"}) are indicated with a star


likely to be enriched for core regulators. Amongst the transcription factors most consistently linked to the ABC-subset is *BATF*, an NFkB target gene that has recently been identified as a key partner of IRF4 [@pone.0055895-Ciofani1], [@pone.0055895-Tussiwand1], [@pone.0055895-Li1], [@pone.0055895-Glasmacher1]. This is of particular interest since ABC-DLBCL and myeloma show non-oncogenic addiction to IRF4 function [@pone.0055895-Yang1], [@pone.0055895-Shaffer3]. IRF4 depends on partner transcription factors to occupy DNA, the canonical partners being ETS-factors SPIB or PU.1 in B-cells; in contrast BATF plays a dominant role in T-cells [@pone.0055895-Ciofani1], [@pone.0055895-Li1], [@pone.0055895-Glasmacher1]. IRF4 is itself an NFkB target gene, which is a principle mechanism proposed for its expression in ABC-DLBCL [@pone.0055895-Shaffer4]. *BATF* expression in ABC-DLBCL may be explained in a similar fashion since it features on multiple NFkB signature lists, including the MSigDB signatureB-cell differentiation, which can co-operate with BLIMP1 in silencing *CIITA* [@pone.0055895-Yoon1]. The latter is essential for MHC class-II expression, and shows a weak class-association with GCB-DLBCL. Expression of ZBTB32 and repression of *CIITA* may thus contribute to immune-evasion in ABC-DLBCL [@pone.0055895-Shaffer4], [@pone.0055895-Rimsza3]. *KCNA3* (also known as Kv1.3) encodes a potassium channel, which is expressed in effector memory T-cells and memory B-cells [@pone.0055895-Cahalan1], [@pone.0055895-Wulff1]. KCNA3 has been identified as a potential target for therapy in autoimmune disease [@pone.0055895-Beeton1], and several strategies for inhibition have been developed in this context [@pone.0055895-Cahalan1]. The strong and consistent expression of *KCNA3* identifies this as an intriguing candidate for a novel therapeutic approach in ABC-DLBCL.

Enrichments of gene signatures derived from previous studies [@pone.0055895-Xie1], [@pone.0055895-Ngo1], [@pone.0055895-Basso1], [@pone.0055895-Lam1], [@pone.0055895-Lam2], [@pone.0055895-Davis1], across meta-profiles and across individual data


the lower panels the results are shown for all individual classifiers, and meta-classifiers on data sets GSE32918, and GSE10846 divided into CHOP and R-CHOP components. For each component of the table classifiers are ordered by their average rank for survival separation (ABC vs GCB). Shown are the classifier identity, the Hazard Ratio (GCB vs ABC as baseline), 95% confidence interval of the hazard ratio, p-value and log rank.

(XLSX)

######

Click here for additional data file.

######

**Overall classifier ranking and Type-III/unclassified assignments by top 3 classifiers.** The upper panel shows a summary of the performance of individual and meta-classifiers. Classifiers are order by their average rank for survival separation between ABC and GCB classes across the datasets GSE32918, and GSE10846 divided into CHOP and R-CHOP components. In the lower paneldata sets are provided. For data sets used in later stages only classes assigned by DAC (LMT_J48_RF100_SMO) trained on Wright et al. data are shown.

(XLSX)

######

Click here for additional data file.

######

**Confidence, threshold and survival.** Shown are the results observed with DAC (LMT_J48_RF100_SMO) using either the highest confidence for class-assignment or a hard threshold of confidence starting from p-value of 0.5 and incrementing in 0.1 steps. Shown are the Dataset identifier, the threshold used (PValCutoff), the resulting % Type-III/unclassified (%Unclassified), and the associated Hazard Ratios, and 95% Confidence Intervals of the Hazard Ratios for GCB vs ABC as baseline.

(XLSX)

######

Click here for additional data file.

######

**ABC/GCB DLBCL Meta-profiles.** Shown are the complete lists of genes differentially expressed between ABC and GCB classes across all data sets. The table


molecular weight of diblock copolymers were measured by gel permeation chromatography (GPC) with THF as an eluent. [Figure 2](#f2-ijms-11-05027){ref-type="fig"} shows the GPC profiles of P(3HT-*b*-3SFT)s, and the obtained molecular weights are integrated in [Table 1](#t1-ijms-11-05027){ref-type="table"}. P(3HT-*b*-3SFT) synthesized by using 1 mol% Ni(dppp)Cl~2~ catalyst, has Mn = 25,600, Mw = 36,200, which are roughly 2.5 times the Mn and Mw of P(3HT-*b*-3SFT) synthesized by using 2 mol% Ni(dppp)Cl~2~ catalyst. This result suggests that the molecular weight of copolymers could be controlled by the amount of Ni(dppp)Cl~2~.

2.3.. Film Characterization of Polymer
--------------------------------------

Thin films of P(3HT-*b*-3SFT) block copolymers and the P3HT homopolymer were fabricated to investigate their optical properties and surface morphologies. Thin films of polymers were prepared by spin coating from *o*-dichlorobenzene (ODCB) on quarts substrates. In the UV-Vis spectra, P(3HT-*b*-3SFT)s,prepared by the 1 mol% and 2 mol% Ni(dppp)Cl~2~ catalysts, and P3HT show the maximum absorption (λ~max~) at 526, 524 and 556 nm, respectively, with a shoulder peak at approximately 600 nm as indicated in [Figure 3](#f3-ijms-11-05027){ref-type="fig"}. The P3SFT homopolymer film has been reported to show λ~max~ of 482 nm \[[@b22-ijms-11-05027]\]. Even though the content of P3SFT in P(3HT-*b*-3SFT) is small, the influence of P3SFT on optical property of P(3HT-*b*-3SFT) is so significant, that the λ~max~ value of P(3HT-*b*-3SFT) shifts toward the λ~max~ of P3SFT homopolymer.

The surface morphology of the thin film of P3HT and P(3HT-*b*-3SFT)s were observed by the atomic force microscopy (AFM). [Figure 4](#f4-ijms-11-05027){ref-type="fig"} shows AFM phase images of thin films of P3HT and P(3HT-*b*-3SFT). Roughness values for all polymers obtained from AFM images are summarized


stirred at reflux under argon for 45 min. This mixture (9) was added to the polymerization mixture of D3HT (8) via a syringe. The mixture was stirred at reflux under Ar for 1 h. The reaction mixture was cooled to room temperature, and then poured into methanol (100 mL) and residue was filtered and purified via Soxhlet extraction successively with methanol, acetone, and chloroform. The chloroform fraction was concentrated under vacuum to give P(3HT-*b*-3SFT) as a purple solid (138.6 mg, 33.3%) (10). P(3HT-*b*-3SFT) synthesized by using 1.0 mol% Ni(dppp)Cl~2~, afforded a 30.0% yield.

3.3.. Film Preparation for Measurement of UV-Spectrum and AFM
-------------------------------------------------------------

To investigate morphology and the optical properties of P(3HT-*b*-3SFT)s and P3HT as a reference, thin films of the polymers were prepared by spin coating from *o*-dichlorobenzene on quartsCGWs.
Radio technologies that are expected to be common in capillary networks include e.g. IEEE 802.15.4 (e.g. with IPv6 over Low power Wireless Personal Area Networks (6LoWPAN) or ZigBee as higher layers), Bluetooth Low Energy or low energy versions of the IEEE 802.11 family (i.e. Wi-Fi). Generally, the CGW is under the control of the operator of the cellular network (even though the cellular network operator not necessarily owns the CGW). There are multiple protocols that can be used for managing the devices in a capillary network, such as Simple Network Management Protocol (SNMP) and Open Mobile Alliance (OMA) Lightweight Implementation (LWM2M). In these structures, multiple MTC devices are controlled by a number of managers, where the managers typically communicate with an agent running at the respective MTC device.
Sending


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        echo 'no' . mysql_error();
        var_dump($db);
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the var_dump gives me
     string 'imt/' (length=4)
 so I know that's the error. The question now is how can I escape this?

A:

I tested your code and it returns no wrong results, but it seems it causes the fact that I have enclosed the PHP tag and write the radio button without any mess with PHP in it. So I get deep into yourrun in fear. They all run off, and Porky's boat was then fallen back to sea. After an encounter with some sea serpents, Porky continues to look at his telescope. After the telescope acts a bit funny, he finally discovers America with grass acting like the sea. A parody version of a Statue of Liberty was shown after Porky jumps all excited. A sign was then shown to the left, saying "Attention paleface! Try our Dandruff Cure, one scalp treatment lasts a lifetime. From the Tom E. Hawke Method". After a moment of staring, a steamboat was then shown with a sign reading "Excursion to see the white men, 30 degrees", where the camera greets the Native Americans. After a moment of showing the Native Americans, the chief


Kamal Ibrahim (soccer)

Kamal Said Ibrahim (Amharic: ካማል ዕብራህም) (born 26 July 1992) is an Ethiopian Australian footballer, who plays for Melbourne Knights FC in the National Premier Leagues Victoria.

Early life
Ibrahim was born in Ethiopia and migrated to Victoria with his mother, three brothers and two sisters in 2003 to escape civil war and conflict.

Club career
Ibrahim played for the VIS before earning a scholarship with AIS in 2009.

Melbourne Heart
In February 2010, he was signed by Melbourne Heart for its inaugural season on a multi-year deal. In August 2010, he was offered a 10-day trial with Polish club Legia Warszawa, which was ultimately unsuccessful. He made his début for Melbourne Heart in September 2010 against Brisbane Roar, suffering a four-nil defeat. He made a total of three appearances for theink for 3D printing. Thanks to reversible binding, the building blocks of the ink can be separated again.

Now, the scientists from Karlsruhe and Brisbane have largely refined their development. As reported in the journal Nature Communications, they have developed several inks, in different colors so to speak, that can be erased independently of each other. This enables selective and sequential degradation and reassembly of the laser-written microstructures. In case of highly complex constructions, for instance, temporary supports can be produced and removed again later on. It may also be possible to add or remove parts to or from three-dimensional scaffolds for cell growth, the objective being to observe how the cells react to such changes. Moreover, the specifically erasable 3D inks allow for the exchange of damaged or


than participants with low mental rotation ability in spatial navigation \[[@B9-brainsci-10-00326],[@B10-brainsci-10-00326]\], wayfinding \[[@B11-brainsci-10-00326]\], orientation, and route learning tasks \[[@B12-brainsci-10-00326]\]. More importantly, Kaltner and Jansen \[[@B13-brainsci-10-00326]\] found that mental rotation performance was enhanced after the presentation of fearful images compared to neutral images. Furthermore, a link between a low performance in visuospatial working memory measured by the Corsi task and topographical disorientation has been suggested (e.g., \[[@B14-brainsci-10-00326],[@B15-brainsci-10-00326],[@B16-brainsci-10-00326],[@B17-brainsci-10-00326],[@B18-brainsci-10-00326]\]). As for the mental rotation task, Palmiero and colleagues \[[@B19-brainsci-10-00326]\] showed that participants' performance at the Corsi task and its walkable version \[[@B20-brainsci-10-00326],[@B21-brainsci-10-00326]\] improved when emotional stimuli were used as compared to the neutral ones. Finally, another cognitive skill that could be considered is the ability to discriminate left from right (left-right discrimination: LRD; \[[@B22-brainsci-10-00326]\]). When navigating through the environment, we arethe use of strategies based on visual-spatial working memory, such as mental rotation and visuospatial working memory. This was supported by several studies, showing that a mildly positive mood improves performance in working memory (e.g., \[[@B19-brainsci-10-00326],[@B41-brainsci-10-00326],[@B42-brainsci-10-00326]\]; for reviews: \[[@B43-brainsci-10-00326],[@B44-brainsci-10-00326]\]) and the performance in tasks that call for creative solutions, innovative problem solving, and coping skills \[[@B45-brainsci-10-00326],[@B46-brainsci-10-00326],[@B47-brainsci-10-00326],[@B48-brainsci-10-00326],[@B49-brainsci-10-00326],[@B50-brainsci-10-00326],[@B51-brainsci-10-00326],[@B52-brainsci-10-00326]\]. The reason for this can be found in the "neuropsychological theory of positive mood" \[[@B53-brainsci-10-00326]\]. According to Ashby and colleagues \[[@B53-brainsci-10-00326]\], the positive mood increases dopamine, which is an important underlying biological mechanism for executive control and working memory (WM).

Another interesting result obtained with this study is represented by the relationships between personality traits and spatial memory tasks. Specifically, as the scores on the agreeableness scale, which is a tendency to be


Top Ten Best Refrigerators Brand in India for fastest cooling user review 2017: – Summer has been begun and now everyone is looking for cold water for drinking purpose and for the other things also which get spoiled easily in the summer so for keep them preserve we need a refrigerator which keeps them fresh for a long time. So this summer will be a quite difficult for you in selecting a good refrigerator for you. Here on our website, we will provide you a list of some good refrigerators which will be best for your home and for your pockets too.

Lg is providing this double door refrigerator with the capacity of 260 Lt. Capacity of this refrigerator is high and also providing the one-year warranty with it.  public function clear()
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Electro-catalytic degradation of phenol on several metal-oxide anodes.
Three kinds of Ti-based multilayer metal-oxide electrode, including Ti/SnO(2)+Sb(2)O(3)/PbO(2), Ti/SnO(2)+Sb(2)O(3)/MnO(x) and Ti/SnO(2)+Sb(2)O(3)/RuO(2)+PbO(2) electrodes, were prepared by thermal decomposition, and SnO(2)+Sb(2)O(3) coatings were produced with a polymeric precursor method (PPM). The conversion of phenol was carried out with these electrodes as anodes under galvanostatic control. Samples during the electrolyses were characterized with UV-vis spectra and chromatography, and chemical oxygen demand (COD) and instantaneous current efficiency (ICE) for phenol degradation were also determined. The results show that phenol can be oxidized and degraded for all of the three anodes, and the oxidation reactions of phenol follow first-order kinetics, but there are considerable differences in the effectiveness and performance of electro-catalytic degradation. Phenol can be degraded relatively fast on the Ti/SnO(2)+Sb(2)O(3)/PbO(2) anode and thedegradation rate of phenol is slower with the Ti/SnO(2)+Sb(2)O(3)/MnO(x) electrode, and the slowest with the Ti/SnO(2)+Sb(2)O(3)/RuO(2)+PbO(2) electrode, whose apparent rate constants are 2.49 x 10(-2), 1.42 x 10(-2) and 9.76 x 10(-3) min(-1), respectively. The rates of electro-catalytic degradation relate to oxygen evolution potential, and the higher the oxygen evolution potential, the better the performance of electro-catalytic degradation. The potential for oxygen evolution at the Ti/SnO(2)+Sb(2)O(3)/PbO(2) anode is highest, then Ti/SnO(2)+Sb(2)O(3)/MnO(x), following Ti/SnO(2)+Sb(2)O(3)/RuO(2)+PbO(2). The accelerated life tests at 60 degrees C and in 1.0 mol L(-1) aqueous H(2)SO(4) with an anodic current density of 4.0 Acm(-2) show that the service life is prolonged when the SnO(2)+Sb(2)O(3) interlayer coating are inserted between Ti substrate and active layers.


is no question that petitioner obtained that portion, upon the value of which he is sought to be taxed, because of his standing as an heir and of his claim in that capacity. * * *Whether he would receive any property (as an heir) depended upon the validity of his ancestor's will and the extent to which it would dispose of his ancestor's estate.  When, by compromise and the decree enforcing it, that disposition was limited, what he got from the estate came to him because he was heir * * *.  305 U.S. at 195-197, 59 S.Ct. at 159, 160, 83 L.Ed. at 125-126.

13
The Commissioner contends that taxpayers here acquired their life interest under circumstances analogous to those in Lyeth, that since the nature ofpurchased life interest.  But we think that for income tax purposes these taxpayers must be treated as having acquired their life estates by gift and not by sale or exchange, or purchase.  It is undisputed that whatever claim they may have had to the El Paso stock was acquired by a purported gift.  It was this claim to ownership through an assertedly donative transaction which, among other things, was put in issue by the controversy over the Van Wert estate.  The thrust of taxpayers' position in this controversy was that they were donees.  We cannot conclude otherwise than that, when the dispute was compromised, whatever taxpayers took they took for income tax purposes as donees.

16
Taxpayers stress that, while Lyeth asserted his claim against


relied upon the undisputed and vested character of the wife's community interest, which was exchanged for the life interest.  296 F.Supp. at 528.  Similarly, Sherman Ewing, supra, and C.I.R. v. Matheson, supra, which hold that the discharge of a monetary legacy by the transfer of securities constitutes a sale or exchange of the securities, involve legatees whose right to take was not in dispute.

20
Taxpayers here had no such clearcut right.  The Tax Court held that they had a bona fide claim of title to the stock, but refrained from holding that they were undisputed owners by virtue of the purported gift.  Their claim of ownership was very much in dispute, and by the settlement reached taxpayers relinquished any and all claims of fee simpletitle to the stock.  Under the circumstances we condlude that the exchange of stock for life estate was realistically a compromise of taxpayer's disputed right to the stock,8 and since they claimed the stock as donees they must be treated for federal income tax purposes as having acquired the life estate in that capacity.  We need not, and do not, hold that Lyeth governs transactions such as this unless the right to that which is exchanged is beyond cavil-- the dispute over the purported gift to these taxpayers was more than merely colorable.  We hold only that where there exists a substantial controversy in which a taxpayer claims as a donee, what is received in settlement is received for tax purposes as a donee.

21
Taxpayers urge


as Harte v. United States, 252 F.2d 259 (2d Cir. 1958); James F. Edwards, 37 T.C. 1107 (1962); and Darthey Williams, 36 T.C. 195 (1961) relied upon by taxpayers, involve a construction of the statutory terms 'property' and 'income from property' under 22(b) (3) of the 1939 Code10 and do not affect our conclusion here, which is based upon a more general, nonstatutory determination, of whether taxpayers received a 'part of the very thing claimed.'

23
The final string to taxpayers' bow is the assertion that, since a federal gift tax was imposed on the value of their joint life interest for the year 1957, our disposition is prejudicial to them.  In taxpayers' words 'the Commissioner, having collected a gift tax on the 1957 gift, a refund of which1957 was credited against and reduced the amount of federal tax payable on the Van Wert estate,12 see 26 U.S.C. 2012, so that any gift tax refund to which the estate conceivably might have been entitled would have been offset by an identical increase in the estate tax payable.  We conclude that the payment of a federal gift tax for the year 1957 does not prejudice taxpayers, and in no way affects our ruling with respect to their income tax liability for the years 1962-64.13

24
Since, under the rationale of Lyeth v. Hoey, taxpayers must be treated for income tax purposes as having acquired their joint life estate by gift, 273 of the Code prohibits any deductions for amortization of the cost basis of the life estate.


Conklin pens in 2019. The rose gold nib and trim really balanced out the rich brown barrel. It was also a turning point and kicked off a new and iterative improvements to the unique Omniflex nib.

One color wasn’t enough for this year’s special edition LAMY Safari as they debuted three new pastel colors: Blue Macaron, Powder Rose, and Mint Glaze! The pastel tone was on trend in 2019, but Blue Macaron was definitely the best selling of the bunch. There was no matching ink this year, but the pens look great on their own.

TWSBI’s flagship model, the 580/580AL, received a couple special edition colors this year but none did as well as Emerald when it was launched in February. This was actually our best selling special edition inspread filmed her journey and evacuation flight home with her 8-year-old daughter.

Priscilla Dickey filmed and photographed her journey to the US from the city of Wuhan, the epicenter of the outbreak, which included being picked up by a cab driver in a hazmat suit, deserted city streets, and an airport filled with people wearing masks.

Dickey’s footage, shared with CNN, shows her being driven through the city of 11 million people, which appears almost completely empty as it undergoes a lockdown and its public transport links are severed, and a plane full of masked passengers.

At one stage, before boarding her flight chartered by the US State Department, Dickey says to the camera while wearing a mask: “Now, it’s starring to finally hit me that I’m going to go America.”

She


study was approved by the local ethics committee, and all subjects gave a written informed consent for participation.

Figure 1Flowchart of the study population. Abbreviation: CMR: cardiac magnetic resonance.

Since this study included a correlation between echocardiography and CMR, not all variables were used in the analysis. We will describe the variables that can be acquired by echocardiography and the 3D model-based volumetric assessment of diastolic function using CMR.

Echocardiography
----------------

Echocardiograms were obtained by expert sonographers according to the recommendations of the American Society of Echocardiography (ASE).^[@r10]^ The examinations were reviewed offline by two readers. Readers 1 (A.L.C.A.) and 2 (A.C.A.) had 20 and 5 years of experience, respectively, in reading echocardiograms. Two-dimensional (2D) echocardiograms were recorded using an Aplio scanner (Toshiba Medical Systems Corp, Tochigi, Japan). The images were acquired fromwere acquired on a 1.5 T scanner (Avanto, Siemens, Malvern, PA, USA) using a 2D SSFP acquisition in vertical long-axis, horizontal long-axis, and short-axis orientations with the following parameters: TE 1.16 ms, TR 3.2 ms, flip angle 60°, receiver bandwidth ±1220 kHz, FOV 36 cm, slice thickness 8 mm, slice gap 2 mm, acquisition matrix 205 × 256, number of averages = 1, number of frames = 30. The mean reconstructed temporal resolution (R-R interval/number of cardiac phases) was 30.43 ± 5.44 ms.

CMR images were analyzed using a research version of the CIM 6.2 program modified to assess diastolic function (Auckland MRI Research Group, University of Auckland, New Zealand).^[@r19]^ CMR image analyses were done by two readers accredited by the Auckland MRI Research Group. Readers 1 (M.S.N.) and


by CMR showed trends toward diastolic dysfunction severity similar to those obtained by echocardiography (p \< 0.05). The E/A ratio by CMR was 1.10 ± 0.38 in the normal group, and was lower in the impaired group (1.01 ± 0.26) and higher in the reduced diastolic function group (1.33 ± 0.45, p = 0.03). All other variables showed no difference between groups ([Table 2](#t2){ref-type="table"}).

######

Diastolic measurements by echocardiography and cardiac magnetic resonance

                                     Normal n = 66 (64.70%)   Type I n = 21 (20.60%)   Type II n = 15 (14.70%)The ratio between the early peak filling (E) and atrial peak filling rate (A) using velocity (cm/s) by echocardiography and flow (mL/s) by CMR. (A) Linear regression and Pearson\'s correlation; (B) Bland-Altman analysis.

Values of e\' by tissue Doppler and E\' for the lateral mitral annulus displacement were positively correlated (r = 0.26, p = 0.007), as were E/e\' by CMR and echocardiography (r = 0.24, p = 0.01). However, both septal measurements were not correlated (p \> 0.05).

Prediction of reduced diastolic function by cardiac magnetic resonance
----------------------------------------------------------------------

[Table 4](#t4){ref-type="table"} shows the ROC curve analysis for reduced diastolic function for all CMR parameters. CMR-determined NE and DT were able to predict diastolic dysfunction (AUCs = 0.70 and 0.72, respectively). In addition, the lateral E/E\' ratio appeared to be useful in the


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  Bárbara Sistemas (Spanish branch company of GDELS), Indra and Sapa — are already developing a first research and development (R&D) contract of €89.2 million (US $99 million) in a temporary joint venture basis called "UTE VCR 8x8". Other R&D contracts will be approved in 2018 with the same budget.

The R&D program is developing six different technological projects related to security measures, situational awareness, long-range vision, fuel efficiency for engines, and command and control.

The objective of this national program is to obtain an 8x8 wheeled armored vehicle to replace the obsolete 6x6 wheeled Pegaso BMR after 40 years of service.

"The 8x8 armored fighting vehicle will be useful for today's hybrid threat environments, or for the vast majority of scenarios to which current security challenges will lead us. It is


The specter of a blood pressure J curve arose again last week at the ACC meeting in an analysis of 5,000 patients with diabetes and coronary artery disease in the INVEST trial, who showed a clear, increased rate of death when their antihypertensive treatment dropped their systolic blood pressure below 115 mm Hg (see photo)

One of the best recent analyses to show evidence for the J curve was a 2006 report that used data collected in that same 22,000-patient INVEST study, although the older analysis used data from all patients, not just the ones with diabetes, and focused on the link between low diastolic pressure and both death and myocardial infarction. The 2006 report said that patients faced risk when their diastolic pressure fell below 70 mm Hg.

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Probabilistic programming allows for flexible specification of Bayesian statistical models in code. PyMC3 is a new, open-source probabilistic programmer framework with an intuitive, readable and concise, yet powerful, syntax that is close to the natural notation statisticians use to describe models. It features next-generation fitting techniques, such as the No U-Turn Sampler, that allow fitting complex models with thousands of parameters without specialized knowledge of fitting algorithms.

PyMC3 has recently seen rapid development. With the addition of two new major features: automatic transforms and missing value imputation, PyMC3 has become ready for wider use. PyMC3 is now refined enough that adding features is easy, so we don’t expect adding features in the future will require drastic changes. It has also become user friendly enough for a broader audience. Automatic"that;s not a big deal its all open forest." "we will get a small hotel over there." "I was thinking if they get the info from you laptop." "its password protection so they don;t even sale it." "Its long story i will tell you when i meet you" "let me hell out of here." "its red tomatto place junjun station" "our room is 301 eat if you are hungry do you want some." "I am hungry what is in dinner." "is there are buffe in groud lawn today is party in honeymoon lawn" "chew it" "its really good." "send it to me" "you become fresh I will check outside." "your husband is coming he will come after two hours." "can i order dinner how much you eat?" "think


{#acm20001aj-sec-0002}
=========================

Using a common phantom, CIRS model 801‐P‐B Virtually Human Male Pelvis phantom (Computerized Imaging Reference Systems, Inc., Norfolk, VA), a series of CBCT images with variable exposure were collected on each linac imaging system (see [Table 1](#acm20001aj-tbl-0001){ref-type="table-wrap"}). All images were imported to the XVI software v4.5 and multiple initial offsets and automatic image registrations then applied. The residual registration error from the ground truth was analyzed per image series, with ground truth being taken here as the systematic error (mean registration error).

######

Parameters of imaging systems.

  *Treatment System*                      *\# Image Sets*               *Voxelclinical dose range for prostate IGRT images (10--25 mGy), all three imaging systems performed similarly and within typically acceptable clinical specifications. From this phantom study, automatic image matching uncertainty is acceptable in the majority of cases ($> 90\%$) for regular targets such as the prostate, in contrast to anecdotal use of these systems.[^(13)^](#acm20001aj-bib-0013){ref-type="ref"} It is difficult to generalize this to (nonrigid) clinical patients. Additionally, no difference in automatic registration performance was found between pitch settings of TomoTherapy MVCT although there is substantial time required to obtain higher‐pitch images. The increased z‐resolution may be unnecessary for image matching purposes.

At very‐low dose (1.2 mGy) there was limited signal in the image, making manual matching quite difficult. The automatic image registration had poor results compared to higher doses; however, it still


factors are held constant.

This work has been on a prostate phantom. In situations where the contrast of the target mask might be improved, such as a lung phantom incorporating low density lung with higher density tumor, translation uncertainty would be expected to be reduced by sharpening the minima for the similarity metric.[^(17)^](#acm20001aj-bib-0017){ref-type="ref"} The fine anatomical detail present in patient images compared to bulk homogenous regions of a phantom may also improve the performance of the similarity metric and reduce uncertainty. But in practice this benefit is likely to be lost due to CBCT image quality and the nonrigid nature of patients over the treatment course, with strong contrast objects such as gold fiducial markers and calcifications often driving registrations.

The use of prefiltering projection images prior to CBCT reconstructionserved as transcriptional regulator in cancer significant signal pathways \[[@CR40]\]. To our best knowledge, our study is the first one to evaluate the expression of miR-375 in CRC tissue and matched plasma samples. The results suggest that plasma miR-375, whose expression is consistent between tissue samples and plasma samples, could serve as a minimally invasive biomarker for CRC detection. MiR-375 appears to provide us a way to detect disease by using easily available clinical specimens. However, there were no significant correlations between the expression level of miRNAs in plasma or tissue samples and the clinicopathological features.

Unexpectedly, while miR-206 and miR-125b were down-regulated in tissue samples, they were up-regulated in plasma samples. The search for a possible explanation revealed that miR-206 is a circulating muscle-specific miRNA. The expression of


if she didn't really record the calls, how did you know—"

"A good guess, guv. He _did_ ring her that day, I had proof of that. The cat being ill the very next morning seemed a bit too convenient, if you know what I mean."

"So did he deny it?"

"No, funny enough. I suggested that he'd told her to bring money to the surgery, then when she didn't, he arranged to meet her again that evening. That knocked him for a loop. Mr. Kelly couldn't shut him up after that."

"You must have guessed right about the call. I can't imagine anything else putting the fear of God into him."

Franks allowed himself a small smile. "He said two thousand pounds was nothing to her, pin money, and he needed it tomachine and many scraps and bolts of colorful fabrics.

"You didn't know this was my mother?" asked Wesley, looking utterly baffled. "You didn't come to see me?"

"No, it's something else entirely," said Gemma. "We wanted to talk to your mother about your uncle, Ronald Thomas."

"The stew can wait, Mama." Wesley moved a bolt of red beaded satin from a chair and sat down. "I want to hear this, too."

"Didn't you tell me you had an uncle that was a photographer?" asked Gemma. "Was it by any chance this uncle?"

"Yeah. He was brilliant, my uncle Ronnie. But what you want to know about him for?"

"It's his wife, actually," Kincaid explained. "We thought your mother might be able to tell us something about her background."

"Angel?" whispered Mrs. Howard. When they looked


Of having certain iterations of the series having a darker, more serious tone rather than the happy-go-lucky Avenger humor. It's nice to have the bad guys actually do bad things, rather than just fire off cheap snark.

I dunno though. When it comes down to it, I just liked watching Vader chop people up in a spooky room and watching ships blow up.

So you liked the last 10 minutes then? The rest of the movie was a sub par snore fest with the "dark" elements only being seen right before the credits. I too would have liked the "dark" attempt at a starwars film if it wasn't padded out by some of the most ******* boring characters I have ever seen from a starwars film (baring like phantom menace),it was exactly this one or not.

I enjoyed the entirety of the film greatly but man... It had been years since I actually was frightened by Darth Vader. And when the rebels made the jump to lightspeed and ending up slamming into a Star Destroyer , I was just blown away.

that scene and the death star eclipse are some of the coolest things in all of the movies i also like "be careful not choke on your aspirations" because it was the best ********* pun in the whole franchise

person is saying how beautiful AAA title games are, and how complex/a lot of work is done on making them look that way. Says that one person making a game like this would take a lifetime making one level.


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For most, Christmas comes the same time every year. But for 9-year-old Jacob Thompson, a cancer patient with Stage 4 High Risk Neuroblastoma, the festive day is arriving early — and it will be his last. According to the GoFundMe page set up by Jacob's mother, the family admitted him to Barbara Bush Children's Hospital on October 11 with the understanding that he would pass away within a month.Jacob has been fighting Neuroblastoma, cancer that forms in nerve cells early on, since he was diagnosed at age 5. It has spread to his head and hip, and treatment was deemed unsuccessful. Since Jacob is bed-ridden and has limited time left with his loved ones, they are bringing Christmas to