Reliable solid-state circuits Semiannual report no. 2, Jun. 1 - Nov. 30, 1965

Pulse width modulator and other microminiaturized electronic equipment for space age application

Kissing by the book : carnal knowledge and bookish metaphor in the works of John Donne ; and, The pen, the sword, and the prison key : Lady Mary Wortley Montagu and eighteenth-century suicide discourse

"John Donne, England's premier seventeenth-century metaphysical poet, has long intrigued scholars with the inclusion of elements both sacred and profane in much of his oeuvre. The following essay explores Donne's use of reading and writing in sexual--but nonetheless holy--contexts, primarily in his poetry, but also in his Devotions upon Emergent Occasions. An analysis of these bodily-textual metaphors, in addition to a comparison with similar work by Donne's contemporaries, reveals a distinct trajectory in Donne's work over time. Brazenly rakish in youth, the aging poet returns his pen to the authorial hand of God, a move that signifies not only Donne's growth as an individual but also his talent for metaphorical flexibility. In eighteenth-century England, male poets and scholars alike debated the prevalence, relevance, and ethics of suicide. The following essay attempts to place Lady Mary Wortley Montagu in conversation with her contemporaries, drawing primarily upon her 1736 verses on self-murder, "Address'd To--." Recurring elements of self-destruction and voluntary death in Montagu's work and life indicate her desire to be a part of this critical discourse. Because she did not take her own life--an event which surely would have broadcast her position--it remains for scholars to revisit Montagu's works in light of other eighteenth-century suicide tracts in order to recover her message. Doing so reveals Montagu's ability to surpass the logic of her male contemporaries by demonstrating that suicide can be a rational act of individual liberty, independent of any higher power."--Abstract from author supplied metadata

Ethics of Emerging Communication and Collaboration Technologies for Children

This SIG will provide child-computer interaction researchers and practitioners, as well as other interested CSCW attendees, an opportunity to discuss topics related to the ethics of emerging communication and collaboration technologies for children. The child-computer interaction community has conducted many discussions on ethical issues, including a recent SIG at CHI 2023. However, the angle of communication and collaboration has not been a focus, even though emerging technologies could affect these aspects in significant ways. Hence, there is a need to consider emerging technologies, such as extended reality, and how they may impact the way children communicate and collaborate in face-to-face, remote, and hybrid (mixed-presence) contexts. This SIG will be an opportunity to discuss methods to consider these ethical concerns, properties of emerging technologies that may affect communication and collaboration, considerations for deployment of these emerging technologies, and future scenarios to ponder

Quantifying the benefits of wetland restoration under projected sea level rise

The capacity of vegetated coastal habitats to mitigate erosion and build elevation in response to sea-level rise (SLR) has led to growing interest in their application as Nature Based Solutions (NBS) for shoreline protection. However, a significant uncertainty in the performance of NBS is how these features will respond to future rates of SLR. In this study, we applied the Sea Level Affecting Marshes Model (SLAMM) to a fringing shoreline wetland complex that is directly adjacent to the primary runway of a regional airport in coastal North Carolina, US. The SLAMM model was run at high spatial resolution (1 m cell size) to investigate the effects of projected SLR by 2100 on the wetland communities and to estimate the potential benefits of a proposed NBS project involving the use of dredged sediment to increase wetland surface elevation. Modeling future habitat extent under three SLR scenarios (i.e., intermediate, intermediate-high, and high) with no land modification reveals a consistent pattern of salt marsh expanding into fresh marsh, salt marsh transitioning to higher elevations, and substantially larger overall extents of intertidal and subtidal habitats within the project footprint at relatively high rates of SLR. Simulations that include the NBS indicate changes in the composition of wetland types over time compared with the no-action scenario. Model results help to better understand the long-term behavior of fringing coastal wetlands and the efficacy of their use as part of coastal resilience strategies

Understanding breast cancer survivors’ information-seeking behaviours and overall experiences:a comparison of themes derived from social media posts and focus groups

Objective: Using two different analysis techniques, this study explored differences and similarities in information-seeking discourse and overall breast cancer experiences between posters to a Reddit board and breast cancer survivor focus groups. Design: This study incorporates two qualitative methods for determining themes in breast cancer survivors’ information-seeking behaviours and overall cancer experiences. First, posts from a breast cancer-specific Reddit community were extracted and analysed using the meaning extraction method (MEM) to determine core themes. Then, investigators performed a thematic analysis of two focus groups of breast cancer survivors (N = 18). Finally, themes derived from each analysis method were compared. Main Outcome Measures: Outcome measures include themes extracted from Reddit posts and themes generated from breast cancer survivor focus groups. Results: Findings between qualitative methodologies represent similar yet nuanced themes in survivors’ discourse. The MEM resulted in seven themes: diagnosis, treatment process, social support, existentialism, risk, information-seeking and surgery. Focus groups revealed the same initial four MEM themes plus the following: disclosure, coping and fears. Conclusions: The MEM is a cost-effective research mechanism for informing common themes of experiences of cancer patients and survivors and may offer initial data to guide psychosocial oncology research design and recruitment

Sequential design of computer experiments for the estimation of a probability of failure

This paper deals with the problem of estimating the volume of the excursion set of a function $f:\mathbb{R}^d \to \mathbb{R}$ above a given threshold, under a probability measure on $\mathbb{R}^d$ that is assumed to be known. In the industrial world, this corresponds to the problem of estimating a probability of failure of a system. When only an expensive-to-simulate model of the system is available, the budget for simulations is usually severely limited and therefore classical Monte Carlo methods ought to be avoided. One of the main contributions of this article is to derive SUR (stepwise uncertainty reduction) strategies from a Bayesian-theoretic formulation of the problem of estimating a probability of failure. These sequential strategies use a Gaussian process model of $f$ and aim at performing evaluations of $f$ as efficiently as possible to infer the value of the probability of failure. We compare these strategies to other strategies also based on a Gaussian process model for estimating a probability of failure.Comment: This is an author-generated postprint version. The published version is available at http://www.springerlink.co

NIM811 (N-Methyl-4-isoleucine Cyclosporine), a Mitochondrial Permeability Transition Inhibitor, Attenuates Cholestatic Liver Injury but Not Fibrosis in Mice

Cholestasis causes hepatocyte death, possibly due to mitochondrial injury. This study investigated whether NIM811, an inhibitor of the mitochondrial permeability transition (MPT), attenuates cholestatic liver injury in vivo. Cholestasis was induced in mice by bile duct ligation (BDL). NIM811 was gavaged (20 mg/kg) before BDL and daily (10 mg/kg) afterwards. Mitochondrial depolarization, cell death and MPT onset were assessed by intravital confocal/multiphoton microscopy of rhodamine 123 (Rh123), propidium iodide (PI) and calcein. After BDL, serum alanine aminotransferase (ALT), hepatic necrosis and apoptosis all increased. NIM811 decreased ALT, necrosis and apoptosis by 60 to 86%. In vehicle-treated mice at 6 h after BDL, viable hepatocytes with depolarized mitochondria were 18/high power field (hpf), and non-viable cells were ∼1/hpf, showing that depolarization preceded necrosis. Calcein entered mitochondria after BDL, indicating MPT onset in vivo. NIM811 decreased depolarization by 72%, prevented calcein entry into mitochondria and blocked release of cytochrome c. Hepatic TNFα, TGF-β1 and procollagen α1(I) mRNA, α-smooth muscle actin, and Sirius red staining for collagen increased after BDL but were not different in vehicle- and NIM811-treated mice. Taken together, NIM811 decreased cholestatic necrosis and apoptosis but did not block fibrosis, indicating that the MPT plays an important role in cholestatic cell death in vivo

Using estrus detection patches to optimally time insemination improved pregnancy risk in suckled beef cows enrolled in a fixed-time artificial insemination program

Citation: Hill, S. L., Grieger, D. M., Olson, K. C., Jaeger, J. R., Dahlen, C. R., Bridges, G. A., . . . Stevenson, J. S. (2016). Using estrus detection patches to optimally time insemination improved pregnancy risk in suckled beef cows enrolled in a fixed-time artificial insemination program. Journal of Animal Science, 94(9), 3703-3710. doi:10.2527/jas2016-0469A multilocation study examined pregnancy risk (PR) after delaying AI in suckled beef cows from 60 to 75 h when estrus had not been detected by 60 h in response to a 7-d CO-Synch + progesterone insert (CIDR) timed AI (TAI) program (d-7: CIDR insert concurrent with an injection of GnRH; d 0: PGF(2 alpha) injection and removal of CIDR insert; and GnRH injection at TAI [ 60 or 75 h after CIDR removal]). A total of 1,611 suckled beef cows at 15 locations in 9 states (CO, IL, KS, MN, MS, MT, ND, SD, and VA) were enrolled. Before applying the fixed-time AI program, BCS was assessed, and blood samples were collected. Estrus was defined to have occurred when an estrus detection patch was >50% colored (activated). Pregnancy was determined 35 d after AI via transrectal ultrasound. Cows (n = 746) detected in estrus by 60 h (46.3%) after CIDR removal were inseminated and treated with GnRH at AI (Control). Remaining nonestrous cows were allocated within location to 3 treatments on the basis of parity and days postpartum: 1) GnRH injection and AI at 60 h (early-early = EE; n = 292), 2) GnRH injection at 60 h and AI at 75 h (early-delayed = ED; n = 282), or 3) GnRH injection and AI at 75 h (delayed-delayed = DD; n = 291). Control cows had a greater (P < 0.01) PR (64.2%) than other treatments (EE = 41.7%, ED = 52.8%, DD = 50.0%). Use of estrus detection patches to delay AI in cows not in estrus by 60 h after CIDR insert removal (ED and DD treatments) increased (P < 0.05) PR to TAI when compared with cows in the EE treatment. More (P < 0.001) cows that showed estrus by 60 h conceived to AI at 60 h than those not showing estrus (64.2% vs. 48.1%). Approximately half (49.2%) of the cows not in estrus by 60 h had activated patches by 75 h, resulting in a greater (P < 0.05) PR than their nonestrous herd mates in the EE (46.1% vs. 34.5%), ED (64.2% vs. 39.2%), and DD (64.8% vs. 31.5%) treatments, respectively. Overall, cows showing estrus by 75 h (72.7%) had greater (P < 0.001) PR to AI (61.3% vs. 37.9%) than cows not showing estrus. Use of estrus detection patches to allow for a delayed AI in cows not in estrus by 60 h after removal of the CIDR insert improved PR to TAI by optimizing the timing of the AI in those cows

The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation

Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed