Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.

Q: In chronic lymphocytic leukemia (CLL) signals from the B cell receptor (BCR) play a major role in disease development and progression. In this light, new therapies that specifically target signaling molecules downstream of the BCR continue to be developed. While first studies on the selective small molecule inhibitor of Bruton's tyrosine kinase (Btk), Ibrutinib (PCI-32765), demonstrated that Btk inhibition sensitizes CLL cells to apoptosis and alters their migratory behavior, these studies however did not address whether Btk-mediated signaling is involved in the process of CLL leukemogenesis. To investigate the requirement of Btk signaling for CLL development, we modulated Btk expression in the IgH.ET CLL mouse model, which is based on sporadic expression of the simian oncovirus SV40 T-antigen in mature B cells. To this end, we crossed IgH.ET mice on a Btk-deficient background or introduced a human Btk transgene (CD19-hBtk). Here we show that Btk deficiency fully abrogates CLL formation in IgH.ET mice, and that leukemias formed in Btk haplo-insufficient mice selectively expressed the wild-type Btk allele on their active X chromosome. Conversely, Btk overexpression accelerated CLL onset, increased mortality, and was associated with selection of non-stereotypical BCRs into CLL clones. Taken together, these data show that Btk expression represents an absolute prerequisite for CLL development and that Btk mediated signaling enhances leukemogenesis in mice. We therefore conclude that in CLL Btk expression levels set the threshold for malignant transformation.

A: What is the name of Bruton's tyrosine kinase inhibitor that can be used for treatment of chronic lymphocytic leukemia?
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Q: People have been using sound to make music for thousands of years. They have invented many different kinds of musical instruments for this purpose. Despite their diversity, however, musical instruments share certain similarities. All musical instruments create sound by causing matter to vibrate. The vibrations start sound waves moving through the air. Most musical instruments use resonance to amplify the sound waves and make the sounds louder. Resonance occurs when an object vibrates in response to sound waves of a certain frequency. In a musical instrument such as a guitar, the whole instrument and the air inside it may vibrate when a single string is plucked. This causes constructive interference with the sound waves, which increases their amplitude. Most musical instruments have a way of changing the frequency of the sound waves they produce. This changes the pitch of the sounds. There are three basic categories of musical instruments: percussion, wind, and stringed instruments. In Figure Researchers at Lawrence Berkeley National Laboratory are pioneering a new way to recover 100-year-old record- ings. Found on fragile wax cylinders and early lacquer records, the sounds reveal a rich acoustic heritage, including languages long lost. For more information on how to recover recordings, see [Link] MEDIA Click image to the left or use the URL below. URL: Ultrasound has frequencies higher than the human ear can detect (higher than 20,000 hertz). Although we cant hear ultrasound, it is very useful. Uses include echolocation, sonar, and ultrasonography. Animals such as bats, whales, and dolphins send out ultrasound waves and use their echoes, or reflected waves, to identify the locations of objects they cannot see. This is called echolocation. Animals use echolocation to find prey and avoid running into objects in the dark. Figure 20.13 and the animation at the URL below show how a bat uses echolocation to locate insect prey. Sonar uses ultrasound in a way that is similar to echolocation. Sonar stands for sound navigation and ranging. It is used to locate underwater objects such as sunken ships or to determine how deep the water is. A sonar device is usually located on a boat at the surface of the water. The device is both a sender and a receiver (see Figure 20.14). It sends out ultrasound waves and detects reflected waves that bounce off underwater objects or the bottom of the water. If you watch the video at the URL below, you can see how sonar is used on a submarine. The distance to underwater objects or the bottom of the water can be calculated from the known speed of sound in water and the time it takes for the waves to travel to the object. The equation for the calculation is: Distance = Speed Time Assume, for example, that a sonar device on a ship sends an ultrasound wave to the bottom of the ocean. The speed of the sound through ocean water is 1437 m/s, and the wave travels to the bottom and back in 2 seconds. What is the distance from the surface to the bottom of the water? The sound wave travels to the bottom and back in 2 seconds, so it travels from the surface to the bottom in 1 second. Therefore, the distance from the surface to the bottom is: Distance = 1437 m/s 1 s = 1437 m You Try It! Problem: The sonar device on a ship sends an ultrasound wave to the bottom of the water at speed of 1437 m/s. The wave is reflected back to the device in 4 seconds. How deep is the water? Ultrasound can be used to "see" inside the human body. This use of ultrasound is called ultrasonography. Harmless ultrasound waves are sent inside the body, and the reflected waves are used to create an image on a screen. This technology is used to examine internal organs and unborn babies without risk to the patient. You can see an ultrasound image in Figure 20.15. You can see an animation showing how ultrasonography works at this URL: In this QUEST web extra, Stanford University astrophysicist Todd Hoeksema explains how solar sound waves are a vital ingredient to the science of helioseismology, in which the interior properties of the sun

A: use of ultrasound to locate underwater objects
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Q: The complex expression patterns observed for many genes are often regulated by distal transcription enhancers. Changes in the nucleotide sequences of enhancers may therefore lead to changes in gene expression, representing a central mechanism by which organisms evolve. With the development of the experimental technique of chromatin immunoprecipitation (ChIP), in which discrete regions of the genome bound by specific proteins can be identified, it is now possible to identify transcription factor binding events (putative cis-regulatory elements) in entire genomes. Comparing protein-DNA binding maps allows us, for the first time, to attempt to identify regulatory differences and infer global patterns of change in gene expression across species. Here, we review studies that used genome-wide ChIP to study the evolution of enhancers. The trend is one of high divergence of cis-regulatory elements between species, possibly compensated by extensive creation and loss of regulatory elements and rewiring of their target genes. We speculate on the meaning of the differences observed and discuss that although ChIP experiments identify the biochemical event of protein-DNA interaction, it cannot determine whether the event results in a biological function, and therefore more studies are required to establish the effect of divergence of binding events on species-specific gene expression.

A:
Are human enhancers or promoters evolving faster?
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