"Why couldn't we do this more often?": exploring the feasibility of virtual and distributed work in product design engineering.

Lower costs and higher employee satisfaction are some of the benefits driving organizations to adopt dispersed and virtual working arrangements. Despite these advantages, product design engineering teams-those who develop physical products-have not widely adopted this working style due to perceived critical dependence on physical facilities and the belief that it is ineffective to communicate technical details virtually. This paper uses the mass shift in working conditions caused by the COVID-19 pandemic to explore the feasibility of virtual and distributed work in product design engineering. We conducted 20 semi-structured interviews with product design engineers working virtually to uncover current challenges of, and the beginning of promising strategies for, effective virtual engineering work. We categorize and analyze Tangible Design activities, Intangible Design activities, and Communication and Project Management activities throughout the product design process. Contrary to present opinions, we found that much of a product design engineer's work is realizable in a virtual and distributed setting. However, there are still many challenges, especially when attempting Tangible Design activities-those that require physical products and tools-from home. These challenges, missing from existing virtual product design engineering literature, include but are not limited to individuals' lessened sense of accountability, fewer de-risking opportunities before product sign-off, and limited supervision of production staff. Product design engineers described novel strategies that emerged organically to mitigate these challenges, such as creating digital alternatives for engineering reviews and sign-offs and leveraging rapid prototyping. Recent advances in technology, an increased commitment to reducing environmental impact, and better work-life balance expectations from new generations of workers will only push society faster towards a distributed working model. Thus, it is critical that we use this opportunity to understand the existing challenges for distributed product design engineers, so that organizations can best prepare and become resilient to future shocks.

"The Road We Travel": Developing a co-produced narrative for a photovoice project.

WHAT IS KNOWN ON THE SUBJECT?: PhotoVoice as a participatory methodology has been used within mental health to support marginalized communities in addressing the challenges they encounter. The PhotoVoice methodology aims to encourage and foster collaborative and equal partnerships. However, reports of previous projects highlight that not every stage of the process remains participant-centric. There is limited reporting on participant involvement in the latter stages of projects, such as exhibition design. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: It provides a detailed description of the phases involved in planning and executing a mental health PhotoVoice project. It provides an illustration of how collaborative partnerships can extend into the design and construction of a photography exhibition and its narrative. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: PhotoVoice is an ideal methodology for use within the field of mental health nursing as it promotes service user inclusion in research, places value on lived experiences and provides a creative medium through which service users and family members can advocate for themselves and others. PhotoVoice is an effective and creative methodology for disseminating and communicating both the individual and collective outcomes to the general public. When implementing this methodology, clinicians and researchers need to be cognisant of the necessity to include participants as equal partners at every stage, including in the design of photography exhibitions and disseminating the findings to academic and public audiences. ABSTRACT: Introduction PhotoVoice is a participatory methodology in which marginalized communities represent their lived experiences through photography. While the methodology aims to foster partnerships throughout all phases, the literature suggests that in the field of mental health, some phases are often completed without participant involvement. Aims This paper elaborates on how the PhotoVoice method was used to engage service users and family members around their experience of involvement in a co-produced and co-facilitated mental health education intervention, in order to enhance public and policymakers knowledge of the project. Methods Ten participants were recruited and trained in the PhotoVoice method. Participants documented, through photography, their experiences of involvement in the education intervention. Following this, participants came together to co-produce and disseminate the photography exhibition to the public. Results PhotoVoice proved to be a flexible and creative method by which to include marginalized groups. By adhering to the collaborative principles of the methodology, service users and family members can retain decision-making power from the project's inception to its conclusion. Implications for Practice PhotoVoice is ideal for use within mental health nursing as it coincides with the recovery principle of promoting collaborative partnership between service users, family members and clinicians. Mental health nurses work directly with service users and family members throughout their recovery journey. The PhotoVoice methodology is coherent with the recovery principles of empowerment, collaboration and prioritizing the lived experiences of the individual. As such, this methodology has the potential to enhance greatly what mental health nurses can know and understand about the lived experiences of service users and family members. In turn, engaging with the PhotoVoice methodology can provide a platform from which further collaborative engagement between service users, family members and clinicians can take place.

Structural basis of enhanced binding of extended and helically constrained peptide epitopes of the broadly neutralizing HIV-1 antibody 4E10.

Potent, broadly HIV-1 neutralizing antibodies (nAbs) may be invaluable for the design of an AIDS vaccine. 4E10 is the broadest HIV-1 nAb known to date and recognizes a contiguous and highly conserved helical epitope in the membrane-proximal region of gp41. The 4E10 epitope is thus an excellent target for vaccine design as it is also highly amenable to peptide engineering to enhance its helical character. To investigate the structural effect of both increasing the peptide length and of introducing helix-promoting constraints in the 4E10 epitope, we have determined crystal structures of Fab 4E10 bound to an optimized peptide epitope (NWFDITNWLWYIKKKK-NH(2)), an Aib-constrained peptide epitope (NWFDITNAibLWRR-NH(2)), and a thioether-linked peptide (NWFCITOWLWKKKK-NH(2)) to resolutions of 1.7 A, 2.1 A, and 2.2 A, respectively. The thioether-linked peptide is the first reported structure of a cyclic tethered helical peptide bound to an antibody. The introduced helix constraints limit the conformational flexibility of the peptides without affecting interactions with 4E10. The substantial increase in affinity (10 nM versus 10(4) nM of the IC(50) of the original KGND peptide template) is largely realized by 4E10 interaction with an additional helical turn at the peptide C terminus that includes Leu679 and Trp680. Thus, the core 4E10 epitope was extended and modified to a WFX(I/L)(T/S)XX(L/I)W motif, where X does not play a major role in 4E10 binding and can be used to introduce helical-promoting constraints in the peptide epitope.

Increasing transplant mass results in long-term allograft survival and recovery from transplant vasculopathy.

Late allograft rejection due to transplant vasculopathy continues to be a major clinical problem. Increasing the ratio of donor transplant size to recipient weight has been shown to reduce the incidence of late allograft failure. Using a murine pancreas transplant model we have tested the hypothesis that increasing the donor transplant size in a recipient can promote long-term allograft survival by promoting recovery from transplant vasculopathy. Recipients of an allograft that showed extensive vasculopathy were transplanted with a second donor transplant. The effect of the second allograft on the vasculopathy present in the first graft was measured. Transplanting a second allograft reversed all signs of ongoing rejection, including transplant vasculopathy, resulting in long-term survival of the first graft. Vasculopathy was only reversed if the first and second grafts were from the same mouse strain, suggesting an antigen-specific mechanism. However, the recovery of the first graft was not associated with antigen-specific peripheral tolerance.

IL-4 expression delays eosinophil-independent vasculopathy and fibrosis during allograft rejection in the mouse.

Transplant vasculopathy in the mouse is thought to be dependent on IL-4 and mediated by IL-5 and eosinophils, whereas in the rat and human systems, IL-4 is associated with the absence of transplant vasculopathy and down-regulation of a Th1-type response. In this study we tested the possibility that the apparent difference in the role of IL-4 in transplant vasculopathy is related to protocol differences rather than to the species being studied. Using a protocol that closely resembles that used in rat and human studies, we developed a model of transplant vasculopathy in the mouse that is associated with Th1-type cytokines and independent of IL-5 and eosinophil infiltration. In this model IL-4 promotes a significant delay in vasculopathy in the graft (P = 0.04) and a decrease in the incidence of allograft rejection (P = 0.02). The data suggest that the role of IL-4 in transplant vasculopathy can be controlled by the protocol used to treat the transplant recipient.

Regeneration of the ear after wounding in different mouse strains is dependent on the severity of wound trauma.

The replacement and restoration of tissue mass after organ damage or injury in adult higher vertebrates is critical to the architecture and function of the organ. If replacement occurs with scar tissue, this often results in adverse effects on function and growth as well as an undesirable cosmetic appearance. However, certain mammals, such as the MRL/MpJ mouse, have shown a restricted capacity for regeneration, rather than scar tissue formation, after an excisional ear punch wound. To investigate the changes in tissue architecture leading to ear wound closure, initial ear wounding studies with a 2-mm clinical biopsy punch were performed on MRL/MpJ mice, by using C57BL/6 mice as a nonregenerative control strain. In contrast to previously reported studies on mouse ear regeneration, we observed that C57BL/6 mice in fact showed a limited regenerative capacity. One explanation for this difference could be attributed to the method of wounding used; both previous studies on mouse ear regeneration used a thumb punch, whereas our approach was to use a clinical biopsy punch. This approach led us to further investigate whether the severity of trauma applied influenced the rate of wound healing. We, therefore, compared the effects of the sharp clinical biopsy punch with that of a cruder thumb punch, and introduced a third strain of mouse, Balb/c, known to be a slow-healing strain. A new method to quantify ear punch hole closure was developed and a histologic investigation conducted up to 4 months after wounding. Image analysis data showed a reduction in original ear wound area of 85% in MRL/MpJ mice at 4 weeks and of 91.7% over 4 months by using a biopsy punch. In contrast, the crude thumb punch methodology resulted in an increase in wound area of up to 58% in Balb/c ears; thought to be due to increased necrosis of the wound site. All biopsy-punched wound areas plateaued in healing between days 28 and 112. Only 5 of 80 MRL/MpJ mouse ears showed no residual holes macroscopically after 28 days. Histologically, all strains of mice healed their ear wounds in a similar manner involving re-epithelialization, blastema-like formation, dermal extension, blood vessel formation, chondrogenesis, folliculogenesis, and skeletal muscle and fat differentiation. However, all regenerative features were more pronounced and accelerated in MRL/MpJ mice when compared with C57BL/6 and Balb/c biopsy-punched mouse ears.