Search

Abstract Humans continuously modulate their control strategies during walking based on their ability to anticipate disturbances. However, how people adapt and use motor plans to create stable walking in unpredictable environments is not well understood. Our purpose was to investigate how people adapt motor plans when walking in a novel and unpredictable environment. We evaluated the whole-body center of mass (COM) trajectory of participants as they performed repetitions of a discrete goal-directed walking task during which a laterally-directed force field was applied to the COM. The force field was proportional in magnitude to forward walking velocity and randomly directed towards either the right or left each trial. We hypothesized that people would adapt a control strategy to reduce the COM lateral deviations created by the unpredictable force field. In support of our hypothesis, we found that with practice the magnitude of COM lateral deviation was reduced by 28% (force field left) and 44% (force field right). Participants adapted two distinct unilateral strategies, implemented regardless of if the force field was applied to the right or to the left, that collectively created a bilateral resistance to the unpredictable force field. These strategies included an anticipatory postural adjustment to resist against forces applied to the left, and a more lateral first step to resist against forces applied to the right. In addition, during catch trials when the force field was unexpectedly removed, participants exhibited trajectories similar to baseline trials. These findings were consistent with an impedance control strategy that provides a robust resistance to unpredictable perturbations. However, we also found evidence that participants made predictive adaptations in response to their immediate experience that persisted for three trials. Due to the unpredictable nature of the force field, this predictive strategy would sometimes result in greater lateral deviations when the prediction was incorrect. The presence of these competing control strategies may have long term benefits by allowing the nervous system to identify the best overall control strategy to use in a novel environment.

Introduction: The purpose of this study was to identify leadership perspective on the impact of COVID-19 Plastic and Reconstructive Surgery (PRS) residency application cycle in 2020 and its future implications. Methods: A survey was sent to residency program leaders (RPL), consisting of program directors and division chiefs/chairs. The survey was sent weekly for 4 weeks and remained open for 28 days. Results: A total of 156 PRS RPL were emailed. Response rate was 24% (38/156). A total of 68% were division chiefs/chairs, and 42% were program directors. Ten percent were both division chiefs/chairs and program directors. Among them, 78% were male. Eighty-seven percent of RPLs reported changes in the number of away rotations, of which 91% reported less away rotations. Only 27% of programs provided virtual away rotations (VAR), and 88% of RPLs were not comfortable writing letters of recommendation after VARs. Hundred percent of cases reported that VARs influenced whether an applicant received an interview. A total of 24 RPLs (63%) reported no changes in how they viewed applications due to the pandemic. However, 5 (13%) reported USMLE scores were more important, 4 (11%) reported research was more important, and 4 (11%) reported LORs were more important. Sixty-six percent did not feel they relied heavily on home institution candidates. Seventy-six percent found virtual interviews to be effective in evaluating applicants, and 71% reported they would add virtual interviews in future interviews. Conclusions: During the 2020-2021 PRS residency application cycle, fewer away rotations were offered, and formerly in-person activities were moved to virtual platforms. Virtual activities caused difficulty assessing candidates for many residency programs.

Activated B cell enter germinal centers (GC) to become plasma cells and memory B cells. Here the authors show that some memory B cells recycle to GC via CCL-21 mediated chemotaxis to deliver antigens from the lymph node subcapsular sinus (SCS) to potentially contribute to affinity maturation and antigenic drift.

All-trans retinoic acid (ATRA) activation of retinoic acid receptors (RARs) is crucial to an organism’s proper development as established by findings for mouse foetuses from dams fed a vitamin A-deficient diet. ATRA influences decision-making by embryonic stem (ES) cells for differentiation including lineage fate. From studies of knockout mice, RARα and RARγ regulate haematopoiesis whereby active RARα modulates the frequency of decision-making for myeloid differentiation, but is not essential for myelopoiesis, and active RARγ supports stem cell self-renewal and maintenance. From studies of zebrafish embryo development, active RARγ plays a negative role in stem cell decision-making for differentiation whereby, in the absence of exogenous ATRA, selective agonism of RARγ disrupted stem cell decision-making for differentiation patterning for development. From transactivation studies, 0.24 nM ATRA transactivated RARγ and 19.3 nM (80-fold more) was needed to transactivate RARα. Therefore, the dose of ATRA that cells are exposed to in vivo, from gradients created by cells that synthesize and metabolize, is important to RARγ versus RARα and RARγ activation and balancing of the involvements in modulating stem cell maintenance versus decision-making for differentiation. RARγ activation favours stemness whereas concomitant or temporal activation of RARγ and RARα favours differentiation. Crosstalk with signalling events that are provoked by membrane receptors is also important.

Abstract Bio-loggers are widely used for studying the movement and behavior of animals. However, some sensors provide more data than is practical to store given experiment or bio-logger design constraints. One approach for overcoming this limitation is to utilize data collection strategies, such as non-continuous recording or data summarization that may record data more efficiently, but need to be validated for correctness. In this paper we address two fundamental questions—how can researchers determine suitable parameters and behaviors for bio-logger sensors, and how do they validate their choices? We present a methodology that uses software-based simulation of bio-loggers to validate various data collection strategies using recorded data and synchronized, annotated video. The use of simulation allows for fast and repeatable tests, which facilitates the validation of data collection methods as well as the configuration of bio-loggers in preparation for experiments. We demonstrate this methodology using accelerometer loggers for recording the activity of the small songbird Junco hyemalis hyemalis.

The starting point to describing the origin and nature of any cancer must be knowledge about how the normal counterpart tissue develops. New principles to the nature of hematopoietic stem cells have arisen in recent years. In particular, hematopoietic stem cells can “choose” a cell lineage directly from a spectrum of the end-cell options, and are, therefore, a heterogeneous population of lineage affiliated/biased cells. These cells remain versatile because the developmental trajectories of hematopoietic stem and progenitor cells are broad. From studies of human acute myeloid leukemia, leukemia is also a hierarchy of maturing or partially maturing cells that are sustained by leukemia stem cells at the apex. This cellular hierarchy model has been extended to a wide variety of human solid tumors, by the identification of cancer stem cells, and is termed the cancer stem cell model. At least, two genomic insults are needed for cancer, as seen from studies of human childhood acute lymphoblastic leukemia. There are signature mutations for some leukemia’s and some relate to a transcription factor that guides the cell lineage of developing hematopoietic stem/progenitor cells. Similarly, some oncogenes restrict the fate of leukemia stem cells and their offspring to a single maturation pathway. In this case, a loss of intrinsic stem cell versatility seems to be a property of leukemia stem cells. To provide more effective cures for leukemia, there is the need to find ways to eliminate leukemia stem cells.

Some time ago, we proposed a continuum-like view of the lineages open to hematopoietic stem cells (HSCs); each HSC self-renews or chooses from the spectrum of all end-cell options and can then “merely” differentiate. Having selected a cell lineage, an individual HSC may still “step sideways” to an alternative, albeit closely related, fate: HSC and their progeny therefore remain versatile. The hematopoietic cytokines erythropoietin, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, granulocyte/macrophage colony-stimulating factor and ligand for the fms-like tyrosine kinase 3 instruct cell lineage. Sub-populations of HSCs express each of the cytokine receptors that are positively auto-regulated upon cytokine binding. Many years ago, Waddington proposed that the epigenetic landscape played an important role in cell lineage choice. This landscape is dynamic and unstable especially regarding DNA methylation patterns across genomic DNA. This may underlie the receptor diversity of HSC and their decision-making.

Like all cells, hematopoietic stem cells (HSCs) and their offspring, the hematopoietic progenitor cells (HPCs), are highly sociable. Their capacity to interact with bone marrow niche cells and respond to environmental cytokines orchestrates the generation of the different types of blood and immune cells. The starting point for engineering hematopoiesis ex vivo is the nature of HSCs, and a longstanding premise is that they are a homogeneous population of cells. However, recent findings have shown that adult bone marrow HSCs are really a mixture of cells, with many having lineage affiliations. A second key consideration is: Do HSCs “choose” a lineage in a random and cell-intrinsic manner, or are they instructed by cytokines? Since their discovery, the hematopoietic cytokines have been viewed as survival and proliferation factors for lineage committed HPCs. Some are now known to also instruct cell lineage choice. These fundamental changes to our understanding of hematopoiesis are important for placing niche support in the right context and for fabricating an ex vivo environment to support HSC development.

Reversible distributed programs have the ability to abort unproductive computation paths and backtrack, while unwinding communication that occurred in the aborted paths. While it is natural to assume that reversibility implies full state recovery (as with traditional roll-back recovery protocols), an interesting alternative is to separate backtracking from local state recovery. For example, such a model could be used to create complex transactions out of nested compensable transactions where a programmer-supplied compensation defines the work required to "unwind" a transaction. Reversible distributed computing has received considerable theoretical attention, but little reduction to practice; the few published implementations of languages supporting reversibility depend upon a high degree of central control. The objective of this paper is to demonstrate that a practical reversible distributed language can be efficiently implemented in a fully distributed manner. We discuss such a language, supporting CSP-style synchronous communication, embedded in Scala. While this language provided the motivation for the work described in this paper, our focus is upon the distributed implementation. In particular, we demonstrate that a "high-level" semantic model can be implemented using a simple point-to-point protocol.

Over the past 20 years, many thousands of CD-ROM titles were published; many of these have lasting cultural significance, yet present a difficult challenge for libraries due to obsolescence of the supporting software and hardware, and the consequent decline in the technical knowledge required to support them. The current trend appears to be one of abandonment – for example, the Indiana University Libraries no longer maintain machines capable of accessing early CD-ROM titles.In previous work, we proposed an access model based upon networked ‘virtual collections’ of CD-ROMs which can enable consortia of libraries to pool the technical expertise necessary to provide continued access to such materials for a geographically sparse base of patrons, who may have limited technical knowledge.In this paper, we extend this idea to CD-ROMs designed to operate on ‘classic’ Macintosh systems with an extensive case study – the catalog of the Voyager Company publications, which was the first major innovator in interactive CD-ROMs. The work described includes emulator extensions to support obsolete CD formats and to enable networked access to the virtual collection.

The majority of information about science, culture, society, economy and the environment is born digital, yet the underlying technology is subject to rapid obsolescence. One solution to this obsolescence, format migration, is widely practiced and supported by many software packages, yet migration has well known risks. For example, newer formats – even where similar in function – do not generally support all of the features of their predecessors, and, where similar features exist, there may be significant differences of interpretation.There appears to be a conflict between the wide use of migration and its known risks. In this paper we explore a simple hypothesis – that, where migration paths exist, the majority of data files can be safely migrated leaving only a few that must be handled more carefully – in the context of several scientific data formats that are or were widely used. Our approach is to gather information about potential migration mismatches and, using custom tools, evaluate a large collection of data files for the incidence of these risks. Our results support our initial hypothesis, though with some caveats. Further, we found that writing a tool to identify “risky” format features is considerably easier than writing a migration tool.

Emulation has been widely discussed as a preservation strategy for digital documents that depend upon proprietary executables, as well as for legacy programs. The fundamental assumption of this strategy is that an artifact (document or program) will be bundled with any required contemporaneous software in an archival information package (AIP) which can be loaded and executed in an emulation environment by patrons wishing to access the preserved artifact, yet little has been written about how to identify the required components for such an AIP. Even where a digital document was distributed with a binary viewer, there may be dependencies on other software libraries. In this paper we discuss a pilot study that performed dependency analysis for digital materials originally distributed on CD-ROM. In particular, we show how to utilize a small number of existing off-the-shelf libraries to build a tool that can analyze executables within ISO (CD-ROM) images, and then examine the results of applying this tool to a body of archived images.

For millions of legacy documents, correct rendering depends upon resources such as fonts that are not generally embedded within the document structure. Yet there is a significant risk of information loss due to missing or incorrectly substituted fonts. Large document collections depend on thousands of unique fonts not available on a common desktop workstation, which typically has between 100 and 200 fonts. Silent substitution of fonts, performed by applications such as Microsoft Office, can yield poorly rendered documents. In this paper we use a collection of 230,000 Word documents to assess the difficulty of matching font requirements with a database of fonts. We describe the identifying information contained in common font formats, font requirements stored in Word documents, the API provided by Windows to support font requests by applications, the documented substitution algorithms used by Windows when requested fonts are not available, and the ways in which support software might be used to control font substitution in a preservation environment.

Emulation is frequently discussed as a failsafe preservation strategy for born-digital documents that depend on contemporaneous software for access (Rothenberg, 2000). Yet little has been written about the contextual knowledge required to successfully use such software. The approach we advocate is to preserve necessary contextual information through scripts designed to control the legacy environment, and created during the preservation workflow. We describe software designed to minimize dependence on this knowledge by offering automated configuration and execution of emulated environments. We demonstrate that even simple scripts can reduce impediments to casual use of the digital objects being preserved. We describe tools to automate the remote use of preserved objects on local emulation environments. This can help eliminate both a dependence on physical reference workstations at preservation institutions, and provide users accessing materials over the web with simplified, easy-to-use environments. Our implementation is applied to examples from an existing collection of over 4,000 virtual CD-ROM images containing thousands of custom binary executables.

Over the past 20 years, more than 100,000 CD-ROM titles have been published including thousands of collections of government documents and data. CD-ROMs present preservation challenges at the bit level and in ensuring usability of the preserved artifact. We present techniques we have developed to archive and support user access to a collection of approximately 2,900 CD-ROMs published under the Federal Depository Library Program (FDLP) by the United States Government Printing Office (GPO). The project provides web-based access to CD-ROM contents using both migration and emulation and supports remote execution of the raw CD-ROM images. Our project incorporates off-the-shelf, primarily open-source software. The raw data and (METS) metadata are made available through AFS, a standard distributed file system, to encourage sharing among libraries.

We present performance data relating to the use of migration in a system we are creating to provide web access to heterogeneous document collections in legacy formats. Our goal is to enable sustained access to collections such as these when faced with increasing obsolescence of the necessary supporting applications and operating systems. Our system allows searching and browsing of the original files within their original contexts utilizing binary images of the original media. The system uses static and dynamic file migration to enhance collection browsing, and emulation to support both the use of legacy programs to access data and long-term preservation of the migration software. While we provide an overview of the architectural issues in building such a system, the focus of this paper is an in-depth analysis of file migration using data gathered from testing our software on 1,885 CD-ROMs and DVDs. These media are among the thousands of collections of social and scientific data distributed by the United States Government Printing Office (GPO) on legacy media (CD-ROM, DVD, floppy disk) under the Federal Depository Library Program (FDLP) over the past 20 years.