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The "hello, world" example, which appeared in the first edition of K&R, has become the model for an introductory program in most programming textbooks. The program prints "hello, world" to the standard output, which is usually a terminal or screen display.
File input and output (I/O) is not part of the C language itself but instead is handled by libraries (such as the C standard library) and their associated header files (e.g. stdio.h). File handling is generally implemented through high-level I/O which works through streams. A stream is from this perspective a data flow that is independent of devices, while a file is a concrete device. The high-level I/O is done through the association of a stream to a file. In the C standard library, a buffer (a memory area or queue) is temporarily used to store data before it is sent to the final destination. This reduces the time spent waiting for slower devices, for example a hard drive or solid state drive. Low-level I/O functions are not part of the standard C library[clarification needed] but are generally part of "bare metal" programming (programming that's independent of any operating system such as most embedded programming). With few exceptions, implementations include low-level I/O.
A consequence of C's wide availability and efficiency is that compilers, libraries and interpreters of other programming languages are often implemented in C.[45] For example, the reference implementations of Python,[46] Perl,[47] Ruby,[48] and PHP[49] are written in C.
Progress in the detection of early neurodegenerative disease biomarkers in biological fluids, such as CSF, saliva, and blood has advanced dramatically. These advances have been reviewed in detail recently [196, 197]. Potential fluid biomarkers that fall under the main pathophysiological aspects of neurodegeneration including blood tests, protein aggregates, neuroinflammation markers, and cell death markers have been characterized for many diseases [197]. Primary targets for detection include biomarkers of Aβ pathology, tau pathology, α-synuclein pathology, proteins associated with neurodegeneration, and markers of glial reactivity, for example GFAP [196] (Fig. 2). In addition to fluid biomarkers, high-powered neurological imaging has proved to be a potentially powerful tool for detecting early manifestations of neurodegenerative disease. Imaging modalities currently include magnetic resonance imaging (MRI) and positron emission topography (PET) analysis [198]. Novel PET ligand portfolios for specific neurodegenerative diseases, combined with structural analysis using MRI have enabled the further understanding of temporal changes in neuronal tissue in degenerative neurological disorders. However, there is an absence of cell sub-state specific imaging ligands to offer high fidelity imaging to track disease progression or effectiveness of therapies non-invasively in patients.
There is also an urgent need for improved imaging systems for use in the clinic and in research as we push forward with neuro-replacement and neuroprotective strategies. Resolution of the retina at the cellular level will be fundamental in the assessment of the efficacy of neuroprotective treatments. One example is the detection of immune cells and assessment of the neuroinflammatory state of the tissue through high resolution imaging. As discussed, neuroinflammation is an over-arching theme in neurodegeneration. Determining immune cell infiltration into the retina, or state of glial cell responses and reactivity would represent a major stride forward for clinicians and researchers alike when trying to tackle neuroinflammation in neurodegenerative disease. Similarly, although a distant milestone at present, monitoring the engraftment of new cells to restore vision or cognitive function will also rely on advanced imaging systems not yet available. Novel high-resolution in vivo imaging modalities will be necessary to achieve these goals. One challenge this presents from a research perspective is the multidisciplinary nature of the expertise required to build high-resolution imaging systems, and as such, a focus in the future on multidisciplinary collaborations across medical and bioengineering fields will be necessary.
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