This paper discusses how the arrival of born-digital content into archives operating systems and complex digital collections, archives must build upon practices developed over recent decades in the handling of electronic records while also radically reconsidering the extent of acquisition and approaches to access. These changes are discussed within the context of the manuscripts and computers that comprise Salman Rushdie’s personal literary “papers,” which are housed in Emory University’s Manuscript, Archives, and Rare Book Library (MARBL). Early in the development of the Rushdie project, the library made a commitment to approach the material as holistically as possible, to prioritize the integration of paper and digital, and to balance the needs of donors with those of researchers. The paper will outline how the library developed researcher tools that allow concurrent exploration of the paper material and the born-digital material via emulation and item-level, database-driven searches.

In Ontological Terror Calvin L. Warren intervenes in Afro-pessimism, Heideggerian metaphysics, and black humanist philosophy by positing that the "Negro question" is intimately imbricated with questions of Being. Warren uses the figure of the antebellum free black as a philosophical paradigm for thinking through the tensions between blackness and Being. He illustrates how blacks embody a metaphysical nothing. This nothingness serves as a destabilizing presence and force as well as that which whiteness defines itself against. Thus, the function of blackness as giving form to nothing presents a terrifying problem for whites: they need blacks to affirm their existence, even as they despise the nothingness they represent. By pointing out how all humanism is based on investing blackness with nonbeing—a logic which reproduces antiblack violence and precludes any realization of equality, justice, and recognition for blacks—Warren urges the removal of the human from its metaphysical pedestal and the exploration of ways of existing that are not predicated on a grounding in being.

Beginning with his famous 1963 lecture on Foucault, Derrida repeatedly invokes a line from Kierkegaard, often translated from his French as ‘the instant of decision is madness,’ without ever giving a precise reference or subjecting that sentence to anything like a reading in the Derridean sense. This paper tracks some of the unsuspected complexities that emerge when that sentence is located in Kierkegaard and the Pauline tradition to which Kierkegaard is appealing. It is suggested that the singular functioning of this sentence in Derrida nonetheless, in its very failure to read, shows up something of the madness, folly or stupidity at play in Kierkegaard’s thinking, and thus performs in its repetitions something of the unreadability that opens the possibility of reading itself.

Based on Micah Vandegrift’s article What is digital humanities and what’s it doing in the library? and Stewart Varner’s response to that piece, this article offers an overview of the foundational ideals where libraries and digital humanities overlap. The authors lay out practical ways for libraries to involve themselves in this evolving area, especially focused on current strengths of many libraries including commitments to resource accessibility and project development. Finally, this article proposes that the role of the research librarian is evolving in order to effectively integrate the library as a partner in the scholarship of digital humanities.

Designed to meet the needs of all who play a role in the MR imaging process, this book first develops the very important concepts of the physical principles on which MR imaging is based and then builds an understanding of the various methods and techniques that are at the heart of each imaging procedure. It gives special emphasis to image quality and the associated issues of optimizing protocols. Safety concerns are addressed in order to have an informed staff who can take a realistic approach to reducing risk and increasing patient comfort and acceptance. People who know how to apply various imaging options to the wide range of clinical needs will continue to be a vital link in the total MR imaging process: the objective of this book is to help them obtain maximum performance and benefit from the sophisticated MR technology that is available today.

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Jahnke and Asher explore workflows and methodologies at a variety of academic data curation sites, and Keralis delves into the academic milieu of library and information schools that offer instruction in data curation. Their conclusions point to the urgent need for a reliable and increasingly sophisticated professional cohort to support data-intensive research in our colleges, universities, and research centers.

It has been discovered that the transient receptor potential ankyrin 1 (TRPA1) proteins of Boidae (boas), Pythonidae (pythons), and Crotalinae (pit vipers) are used to detect infrared radiation, but the molecular mechanism for detecting the infrared radiation is unknown. Here, relating the amino acid substitutions in their TRPA1 proteins and the functional differentiations, we propose that three parallel amino acid changes (L330M, Q391H, and S434T) are responsible for the development of infrared vision in the three groups of snakes. Protein modeling shows that the three amino acid changes alter the structures of the central region of their ankyrin repeats.

An important question in auditory neuroscience concerns how the neural representation of sound features changes from the periphery to the cortex. Here we focused on the encoding of sound onsets and we used a modeling approach to explore the degree to which auditory cortical neurons follow a similar envelope integration mechanism found at the auditory periphery. Our “forward” model was able to predict relatively accurately the timing of first spikes evoked by natural communication calls in the auditory cortex of awake, head-restrained mice, but only for a subset of cortical neurons. These neurons were systematically different in their encoding of the calls, exhibiting less call selectivity, shorter latency, greater precision, and more transient spiking compared with the same factors of their poorly predicted counterparts. Importantly, neurons that fell into this best-predicted group all had thin spike waveforms, suggestive of suspected interneurons conveying feedforward inhibition. Indeed, our population of call-excited thin spike neurons had significantly higher spontaneous rates and larger frequency tuning bandwidths than those of thick spike neurons. Thus the fidelity of our model's first spike predictions segregated neurons into one earlier responding subset, potentially dominated by suspected interneurons, which preserved a peripheral mechanism for encoding sound onsets and another longer latency subset that reflected higher, likely centrally constructed nonlinearities. These results therefore provide support for the hypothesis that physiologically distinct subclasses of neurons in the auditory cortex may contribute hierarchically to the representation of natural stimuli.

Hypertonicity increases urea transport independently of, as well as synergistically with, vasopressin in the inner medullary collect duct (IMCD). We previously showed that hypertonicity does not increase the level of cAMP in the IMCD, but it does increase the level of intracellular calcium. Since we also showed that hypertonicity increases both the phosphorylation and biotinylation of the urea transporters UT-A1 and UT-A3, this would suggest involvement of a calcium-dependent protein kinase in the regulation of urea transport in the inner medulla. In this study, we investigated whether protein kinase C (PKC), which is present in the IMCD, is a regulator of urea permeability. We tested the effect of PKC inhibitors and activators on urea permeability in the isolated, perfused rat terminal IMCD. Increasing osmolality from 290 to 690 mosmol/kgH2O significantly stimulated (doubled) urea permeability; it returned to control levels on inhibition of PKC with either 10 μM chelerythrine or 50 μM rottlerin. To determine the potential synergy between vasopressin and PKC, phorbol dibutyrate (PDBu) was used to stimulate PKC. Vasopressin stimulated urea permeability 247%. Although PDBu alone did not change basal urea permeability, in the presence of vasopressin, it significantly increased urea permeability an additional 92%. The vasopressin and PDBu-stimulated urea permeability was reduced to AVP alone levels by inhibition of PKC. We conclude that hypertonicity stimulates urea transport through a PKC-mediated phosphorylation. Whether PKC directly phosphorylates UT-A1 and/or UT-A3 or phosphorylates it as a consequence of a cascade of activations remains to be determined.

Experimental and corresponding modeling studies indicate that there is a 2- to 5-fold variation of intrinsic and synaptic parameters across animals while functional output is maintained. Here, we review experiments, using the heartbeat central pattern generator (CPG) in medicinal leeches, which explore the consequences of animal-to-animal variation in synaptic strength for coordinated motor output. We focus on a set of segmental heart motor neurons that all receive inhibitory synaptic input from the same four premotor interneurons. These four premotor inputs fire in a phase progression and the motor neurons also fire in a phase progression because of differences in synaptic strength profiles of the four inputs among segments. Our work tested the hypothesis that functional output is maintained in the face of animal-to-animal variation in the absolute strength of connections because relative strengths of the four inputs onto particular motor neurons is maintained across animals. Our experiments showed that relative strength is not strictly maintained across animals even as functional output is maintained, and animal-to-animal variations in strength of particular inputs do not correlate strongly with output phase. Further experiments measured the precise temporal pattern of the premotor inputs, the segmental synaptic strength profiles of their connections onto motor neurons, and the temporal pattern (phase progression) of those motor neurons all in the same animal for a series of 12 animals. The analysis of input and output in this sample of 12 individuals suggests that the number (four) of inputs to each motor neuron and the variability of the temporal pattern of input from the CPG across individuals weaken the influence of the strength of individual inputs. Moreover, the temporal pattern of the output varies as much across individuals as that of the input. Essentially, each animal arrives at a unique solution for how the network produces functional output.

Abstract Wall Shear Stress (WSS) has been identified as an important factor in the pathogenesis of atherosclerosis. We utilized a novel murine aortic coarctation model to acutely create a region of low magnitude oscillatory WSS in vivo. We employed this model to test the hypothesis that acute changes in WSS in vivo induce upregulation of inflammatory proteins, mediated by reactive oxygen species (ROS). Superoxide generation and VCAM-1 expression both increased in regions of low magnitude oscillatory WSS. WSS-dependent superoxide formation was attenuated by tempol treatment, but was unchanged in p47 phox knockout (ko) mice. However, in both the p47 phox ko mice and the tempol-treated mice, low magnitude oscillatory WSS produced an increase in VCAM-1 expression comparable to control mice. Additionally, this same VCAM-1 expression was observed in ebselen-treated mice and catalase overexpressing mice. These results suggest that although the redox state is important to the overall pathogenesis of atherosclerosis, the initial WSS-dependent inflammatory response leading to lesion localization is not dependent on ROS. Antioxid. Redox Signal. 15, 1369–1378.

The Breast and Cervical Cancer Prevention and Treatment Act program in Georgia creates a quicker pathway for low-income, uninsured women with breast cancer to access services and receive more treatment than women enrolled in traditional Medicaid eligibility groups.

Background Platelet storage adversely affects platelet structure and function in vitro, and is associated with decreased platelet recovery and function in vivo. In pediatric transfusion medicine, it is not uncommon for small residual volumes to remain in parent units following aliquot preparation of leukoreduced apheresis-derived platelets (LR-ADP). However, limited data exists regarding the impact of storage on residual small volume LR-ADP. Study Design and Methods Standard metabolic testing was performed on residual volumes of LR-ADP following aliquot removal and platelet aggregometry using a dual agonist of ADP and collagen was performed on stored, small volume aliquots (10-80 ml) created from an in vitro model of platelet storage. Results 77 LR-ADP underwent metabolic (n=67) or metabolic and aggregation (n=10) studies. All products maintained a pH > 6.89 throughout storage. Lactate and pCO2 increased proportionally with longer storage time. Regardless of acceptable metabolism during storage, aggregation in 10-20 ml aliquots was impaired by day 4 and aliquots less than 40 ml demonstrated the most dramatic decrease in aggregation from baseline. Conclusions Despite maintenance of acceptable metabolic conditions, residual volumes of LR-ADP develop impaired aggregation in vitro that may adversely affect platelet survival and function in vivo. At volumes below 40 ml, LR-ADP revealed reduced aggregation. As a result, it is recommended to monitor and record volumes of LR-ADP used for pediatric transfusion. Moreover, once LR-ADP attain a volume of 50 ml or less on day 4 or 5 of storage, consider discarding these products until their in vivo efficacy can be studied.

Object This study investigates the effect of tumor location on alterations of language network by brain tumors at different locations using blood oxygenation level dependent (BOLD) fMRI and group independent component analysis (ICA). Subjects and Methods BOLD fMRI data were obtained from 43 right handed brain tumor patients. Presurgical mapping of language areas was performed on all 43 patients with a picture naming task. All data were retrospectively analyzed using group ICA. Patents were divided into three groups based on tumor locations, i.e., left frontal region, left temporal region or right hemisphere. Laterality index (LI) was used to assess language lateralization in each group. Results The results from BOLD fMRI and ICA revealed the different language activation patterns in patients with brain tumors located in different brain regions. Language areas, such as Broca’s and Wernicke’s areas, were intact in patients with tumors in the right hemisphere. Significant functional changes were observed in patients with tumor in the left frontal and temporal areas. More specifically, the tumors in the left frontal region affect both Broca’s and Wernicke’s areas, while tumors in the left temporal lobe affect mainly Wernicke’s area. The compensated activation increase was observed in the right frontal areas in patients with left hemisphere tumors. Conclusion Group ICA provides a model free alternative approach for mapping functional networks in brain tumor patients. Altered language activation by different tumor locations suggested reorganization of language functions in brain tumor patients and may help better understanding of the language plasticity.

Urea transporters UT-A1 and UT-A3 are both expressed in the kidney inner medulla. However, the function of UT-A3 remains unclear. Here, we found that UT-A3, which comprises only the NH2-terminal half of UT-A1, has a higher urea transport activity than UT-A1 in the oocyte and that this difference was associated with differences in N-glycosylation. Heterologously expressed UT-A3 is fully glycosylated with two glycoforms of 65 and 45 kDa. By contrast, UT-A1 expressed in HEK293 cells and oocytes exhibits only a 97-kDa glycosylation form. We further found that N-glycans of UT-A3 contain a large amount of poly-N-acetyllactosamine. This highly glycosylated UT-A3 is more stable and is enriched in lipid raft domains on the cell membrane. Kifunensine, an inhibitor of α-mannosidase that inhibits N-glycan processing beyond high-mannose-type N-glycans, significantly reduced UT-A3 urea transport activity. We then examined the native UT-A1 and UT-A3 glycosylation states from kidney inner medulla and found the ratio of 65 to 45 kDa in UT-A3 is higher than that of 117 to 97 kDa in UT-A1. The highly stable expression of highly glycosylated UT-A3 on the cell membrane in kidney inner medulla suggests that UT-A3 may have an important function in urea reabsorption.

Background It is difficult to longitudinally characterize cognitive impairment in amyotrophic lateral sclerosis (ALS) due to motor deficits, and existing instruments aren’t comparable with assessments in other dementias. Methods The ALS Brief Cognitive Assessment (ALS-BCA) was validated in 70 subjects (37 with ALS) who also underwent detailed neuropsychological analysis. Cognitive predictors for poor survival were then analyzed in a longitudinal cohort of 171 ALS patients. Results The ALS-BCA was highly sensitive (90%) and specific (85%) for ALS-dementia (ALS-D). ALS-D patients had shorter overall survival, primarily due to the poor survival among ALS-D patients with disinhibited or apathetic behaviors after adjusting for demographic variables, ALS site of onset, medications, and supportive measures. ALS-D without behavioral changes was not a predictor of poor survival. Conclusion ALS-D can present with or without prominent behavioral changes. Cognitive screening in ALS patients should focus on behavioral changes for prognosis, while non-behavioral cognitive impairments may impact quality of life without impacting survival.