Colorectal cancer (CRC) arises as the consequence of progressive changes from normal epithelial cells through polyp to tumor, and thus is an useful model for studying metabolic shift. In the present study, we studied the metabolomic profiles using high analyte specific gas chromatography/mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) to attain a systems-level view of the shift in metabolism in cells progressing along the path to CRC. Colonic tissues including tumor, polyps and adjacent matched normal mucosa from 26 patients with sporadic CRC from freshly isolated resections were used for this study. The metabolic profiles were obtained using GC/MS and LC/MS/MS. Our data suggest there was a distinct profile change of a wide range of metabolites from mucosa to tumor tissues. Various amino acids and lipids in the polyps and tumors were elevated, suggesting higher energy needs for increased cellular proliferation. In contrast, significant depletion of glucose and inositol in polyps revealed that glycolysis may be critical in early tumorigenesis. In addition, the accumulation of hypoxanthine and xanthine, and the decrease of uric acid concentration, suggest that the purine biosynthesis pathway could have been substituted by the salvage pathway in CRC. Further, there was a step-wise reduction of deoxycholic acid concentration from mucosa to tumors. It appears that to gain a growth advantage, cancer cells may adopt alternate metabolic pathways in tumorigenesis and this flexibility allows them to adapt and thrive in harsh environment.

The choice for adjuvant chemotherapy in stage II colorectal cancer (CRC) is controversial as many patients are cured by surgery alone and it is difficult to identify patients with high-risk of recurrence of the disease. There is a need for better stratification of this group of patients. Mass spectrometry imaging could identify patients at risk. We report here the N-glycosylation signatures of the different cell populations in a group of stage II CRC tissue samples. The cancer cells, compared to normal epithelial cells, have increased levels of sialylation and high-mannose glycans, as well as decreased levels of fucosylation and highly branched N-glycans. When looking at the interface between cancer and its microenvironment, it seems that the cancer N-glycosylation signature spreads into the surrounding stroma at the invasive front of the tumor. This finding was more outspoken in patients with a worse outcome within this sample group.

Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic - and β-emitting isotope ¹⁷⁷Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. Methods: Gemini was synthesized by linking 2 S-2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker. [¹⁷⁷Lu]Lu-Gemini was prepared with no-carrier-added ¹⁷⁷LuCl₃ to a molar-specific activity of 123 GBq/μmol and radiochemical purity of more than 99%. The specificity of BsAb-¹⁷⁷Lu-Gemini was verified in vitro. Subsequently, we evaluated biodistribution and whole-body clearance for [¹⁷⁷Lu]Lu-Gemini and, for comparison, our gold-standard monovalent [¹⁷⁷Lu]Lu-S-2-(4-aminobenzyl)-DOTA ([¹⁷⁷Lu]Lu-DOTA-Bn) in naïve (tumor-free) athymic nude mice. For our proof-of-concept system, a 3-step pretargeting approach was performed with an established DOTA-PRIT regimen (anti-GPA33/anti-DOTA IgG-scFv BsAb, a clearing agent, and [¹⁷⁷Lu]Lu-Gemini) in mouse models. Results: Initial in vivo studies showed that [¹⁷⁷Lu]Lu-Gemini behaved similarly to [¹⁷⁷Lu]Lu-DOTA-Bn, with almost identical blood and whole-body clearance kinetics, as well as biodistribution and mouse kidney dosimetry. Pretargeting [¹⁷⁷Lu]Lu-Gemini to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [¹⁷⁷Lu]Lu-Gemini for blood, tumor, liver, spleen, and kidneys of 3.99, 455, 6.93, 5.36, and 14.0 cGy/MBq, respectively. Tumor–to–normal tissue absorbed-dose ratios (i.e., therapeutic indices [TIs]) for the blood and kidneys were 114 and 33, respectively. In addition, we demonstrate that the use of bivalent [¹⁷⁷Lu]Lu-Gemini in DOTA-PRIT leads to improved TIs and augmented [¹⁷⁷Lu]Lu-Gemini tumor uptake and retention in comparison to monovalent [¹⁷⁷Lu]Lu-DOTA-Bn. Finally, we established efficacy in SW1222 tumor-bearing mice, demonstrating that a single injection of anti-GPA33 DOTA-PRIT with 44 MBq (1.2 mCi) of [¹⁷⁷Lu]Lu-Gemini (estimated tumor-absorbed dose, 200 Gy) induced complete responses in 5 of 5 animals and a histologic cure in 2 of 5 (40%) animals. Moreover, a significant increase in survival compared with nontreated controls was noted (maximum tolerated dose not reached). Conclusion: We have developed a bivalent DOTA-radiohapten, [¹⁷⁷Lu]Lu-Gemini, that showed improved radiopharmacology for DOTA-PRIT application. The use of bivalent [¹⁷⁷Lu]Lu-Gemini in DOTA-PRIT, as opposed to monovalent [¹⁷⁷Lu]Lu-DOTA-Bn, allows curative treatments with considerably less administered ¹⁷⁷Lu activity while still achieving high TIs for both the blood (>100) and the kidneys (>30).

An explosion at a food-coloring factory in Louisville, Ky., hospitalized at least 11, including two in critical condition, on Tuesday afternoon.

An explosion at a food-coloring factory in Louisville, Ky., hospitalized at least 11, including two in critical condition, on Tuesday afternoon.

Small groups of Portland youngsters gathered in gardens, played with plant-based dyes, and cooked up vegan meals as part of Camp ELSO's mission to foster STEM learning for students of color.

The second College Football Playoff rankings dropped on Tuesday night with Oregon retaining its status as the No. 1 team in the country ahead of No. 2 Ohio State and No. 3 Texas. College Football Playoff:

The second College Football Playoff Top 25 rankings were revealed on Tuesday and the now-7-2

Gijs Joost Brouwer
Nov 4, 2009; 29:13992-14003
BehavioralSystemsCognitive

The artists known as OSGEMEOS showcase the largest exhibition of their work in the United States at the Hirshhorn Museum and Sculpture Garden

The work of Diné artist DY Begay, now on view at the National Museum of the American Indian, blends tradition and modernity

Learn more about color blindness: https://www.smithsonianmag.com/smithsonian-institution/ask-smithsonian-how-does-world-look-the-color-blind-180960415/ Have a question in mind? It's your turn to Ask Smithsonian: https://www.smithsonianmag.com/smithsonian-institution/ask-smithsonian/ask-form/

As foliage darkens in the fall, the pigments within the plant matter break down and transform

What happens when one of the nation's largest rivers dries up? Photojournalist Pete McBride tells us about the consequences of a prolonged drought in the Colorado River, which provides drinking water and electricity to millions of Americans, and shares his experience walking the river from end to end. What can we learn from the landscape revealed by the historically low water levels, and will they become the new normal? Read “The Breathtaking Glen Canyon Reveals Its Secrets (https://www.smithsonianmag.com/science-nature/glen-canyon-reveals-its-secrets-180980754/) ,” photographs & text by Pete McBride, Smithsonian, October 2022. Learn more about Pete and his work at his site (https://petemcbride.com/) . There’s More to That is a production of Smithsonian magazine and PRX Productions. From the magazine, our team is Chris Klimek, Debra Rosenberg and Brian Wolly. From PRX, our team is Jessica Miller, Adriana Rosas Rivera, Genevieve Sponsler, Terence Bernardo, and Edwin Ochoa. The Executive Producer of PRX Productions is Jocelyn Gonzales. Episode artwork by Emily Lankiewicz. Music by APM Music.

Two lionfish in Papua New Guinea swim gracefully

Serving 30 million people in seven states and Mexico, the drying Colorado River can still be saved by sustainable measures and collaboration

Feeling blue? Try watching this one-minute video. Our Ask Smithsonian host, Eric Schulze, explains how colors affect our moods.

Experts are carefully uncovering traces of the original paint and fragments of gold leaf that once adorned the 2,000-year-old Temple of Edfu

The viewfinders are outfitted with special lenses that help people with red-green colorblindness distinguish between hues

Unlike other birds, which get pigments from their diets, parrots produce their own—but scientists never fully understood the underlying mechanisms, until now

Apple's new M4 24-inch iMac shows that the all-in-one desktop computer still has a loyal fanbase, with every reviewer also relishing the more vibrant colors of the new model.

Medical imaging is no longer in Kansas, Toto, as a team led by Penn State researchers brings traditional black and white diagnostic images of X-rays and traditional CT scans into technicolor. The researchers developed novel contrast agents that target two proteins implicated in osteoarthritis, a degenerative joint disease commonly characterized as wear-and-tear arthritis.

The Colorado Supreme Court decided Douglas County's Choice Scholarship Program is unconstitutional.

A grizzly bear enjoyed every bit of a recent snow day at the Cheyenne Mountain Zoo in Colorado Springs, Colorado.

Oppo Find X8 series was introduced in China on October 24. Now the company has announced the India launch date of the lineup. The Oppo Find X8 and Oppo Find X8 Pro will launch in India later this month. The availability details and key features of the handsets have been confirmed. Alongside the Oppo Find X8 series, Oppo will also unveil the Android 15-based ColorOS 15 for the global market.

Delaware's Type 6 engine and three-man crew are part of 313 personnel currently fighting the Oil Springs Fire, located 20 miles south of Rangely, Colorado. The fire was started by lightning on June 18 and has grown to 12, 613 acres with only 18 percent containment. Delaware's crew is working on one of the fire's priority areas, Division D, which involves the continued protection of the Dragon Trail Compressor Site. The fire is spreading moderately in a mixture of  pinyon, juniper and sagebrush.  Delaware's crew is comprised of engine boss Samual Topper of Maryland, engine boss trainee Adam Keever of Newark, and FFT2 Bradley Melson of Milford. The crew mobilized from Blackbird State Forest last week and started work on Saturday, June 26.

As a mark of respect for the victims of the senseless acts of violence perpetrated on March 22, 2021, in Boulder, Colorado, President Biden ordered flags at all U.S. government buildings and facilities to be flown at half-staff until sunset on March 27, 2021. In concurrence with the President’s order, Governor Carney has ordered both […]

Read the in depth Review of 1MORE Colorbuds Audio Video. Know detailed info about 1MORE Colorbuds configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.

Hi

In the environment I'm currently working, axes are shown for schematic, symbol, and layout views.For schematics and symbols, I'd prefer a dim gray, such that the axes are just visible but not dominant. For the layout, I'd prefer a brighter color. Is there a way to realize this? So far when I change the color of the 'axis' layer in the display resource editor, the axes in all three views get changed together:

Thanks very much for your input!

Hi,

I'm searching for a way to get a quick overview of too low cpk-values after a montecarlo sim. The non-MC results have the spec and thus the easy/understandable red/green/(yellow) colorcoding, but for MC sims I don't get a highlight for high variations inside the limits.

Is this possible (besides copying each expression into avg()+3*std()) and ..-..)?

It would be really handy to scan through finished sims...

(My final application is then to export the table for my reports and documentation...)

Regards,

leo

Hello,

First, I had something working that broke in the past few versions that I've been meaning to get working again. There was some setting I recall in the GUI that allowed me to have inputs be placed in the waveform viewer with yellow traces, and output signals with orange traces to match the name colors. How can I set this to happen in the .simvisionrc file?

Second, I would like to add something to my .simvisionrc file to go through foreach signal and depending on key locations based on the signal's Path.Name (mainly the model and design areas) such that if the path contains "mon", then to auto-set the trace and name colors to something such as cyan. I'd like to have loops for various key areas of the design to color-code the signals.

Third, I am interested if there is a possibility of coloring names/traces foregound colors to based on which position they are in the waveform viewer to make banding, ideally such that every three (or whatever) are one color (or a color mutation, adding some gray to signals colorized by the auto-coloring mentioned already, etc) that allows for the signal names/traces to be colorized along with the built-in optional black/gray background banding.

Thanks in advance

Colorado voters on Tuesday rejected Proposition 131, which would have upended the way elections are conducted in the state and moved the state to a ranked-choice voting system.

Prop. KK will create an excise tax on firearms and ammunition, primarily to pay for victim services.

Coloradans have rejected a proposed ban on mountain lion and bobcat hunting -- a hit for wildlife advocates who have worked to outlaw or change the practice for years.

Colorado voters will decide whether to repeal the state constitution's now-defunct marriage definition that only recognizes unions between a man and a woman.

Colorado Democrats looked set to maintain their supermajority in the state House as of Wednesday afternoon, though they fell short of reaching the same threshold in the Senate.

This is the third presidential election in a row that the state's voters have rejected Trump -- after going in 2016 for Hillary Clinton, and in 2020 for President Joe Biden.

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