cssi/SciSciGPT-SciSciNet huggingface dataset:
Opposing roles for distinct LINC complexes in regulation of the small GTPase RhoA

Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes span the nuclear envelope and transduce force from dynamic cytoskeletal networks to the nuclear lamina. Here we show that LINC complexes also signal from the nuclear envelope to critical regulators of the actin cytoskeleton. Specifically, we find that LINC complexes that contain the inner nuclear membrane protein Sun2 promote focal adhesion assembly by activating the small GTPase RhoA. A key effector in this process is the transcription factor/coactivator complex composed of SRF/Mkl1. A constitutively active form of SRF/Mkl1 was not sufficient to induce focal adhesion assembly in cells lacking Sun2, however, suggesting that LINC complexes support RhoA activity through a transcription-independent mechanism. Strikingly, we also find that the inner nuclear membrane protein Sun1 antagonizes Sun2 LINC complexes and inhibits RhoA activation and focal adhesion assembly. Thus different LINC complexes have opposing roles in the transcription-independent control of the actin cytoskeleton through the small GTPase RhoA.
New cardiac magnetic resonance imaging modalities aid in the detection of myocardial fibrosis.

Heart failure (HF) is the end stage of many cardiovascular diseases, in which left ventricular (LV) function and structural remodeling are unable to meet the body's cardiac‐output demand. The burden of HF has reached an epidemic scale, with more than 20 million individuals affected worldwide (Roger 2013). Despite dramatic improvements in the clinical management of this disease, our ability to identify HF in its early stages and appropriately risk‐stratify patients for suitable treatments remains limited. As such, there has been an ongoing search for new and improved biomarkers to help us identify early disease and categorize HF into its various stages, while in tandem, advancements in imaging methods are improving our detection of structural and functional derangements resulting from various etiologies. The collective outcome of such efforts will be an improved ability to diagnose, stage, risk‐stratify, and manage HF from early subclinical manifestations to the full‐blown syndrome. In this study, Lottonen‐Raikaslehto and colleagues (Lottonen‐Raikaslehto et al. 2017) demonstrate that the cardiac magnetic resonance (CMR) imaging modality, T1 longitudinal relaxation in the rotating frame (known as T1 ρ ), can be potentially used as a sensitive method to detect diffuse fibrosis in the heart, indicating that this technique may be a valuable addition to the …
Development and Initial Evaluation of the Psychometric Properties of the Dialectical Behavior Therapy Barriers to Implementation Scale (BTI-S).

OBJECTIVE We examined the psychometric properties of the Dialectical Behavior Therapy (DBT) Barriers to Implementation Scale (BTI-S). METHOD Participants were clinicians completing a bipartite training, separated by 6 months of self-study, to implement DBT. Exploratory factor analysis was conducted with data collected from the initial training period (N = 790), while confirmatory factor analysis was based on data from the final training period (N = 660). RESULTS The final model included 26 items and 4 factors with overall acceptable fit, χ2 (293, N = 660) = 460.989, p < .001, comparative fit index = .909, Tucker-Lewis index = .899, root mean square root mean square error of approximation (90% confidence interval) = .015. The internal reliability of the scores was low (range = .56 to .72). CONCLUSION The final model fits reasonably well and measures four domains considered important for implementation of DBT. However, the low reliability of the scores indicates that the BTI-S would be improved with further development.
Postmortem X-ray Computed Tomography (CT) and Forensic Autopsy: A Review of the Utility, the Challenges and the Future implications:

The utility of computed tomography (CT) for forensic autopsy is being defined. Small studies have indicated potential areas of use. Systematic studies are few. Evidence of the utility of CT as an a...
Finite Element/Difference Modeling of Electroceramics

The hydrostatic piezoelectric response of PZT composites and the electric field distribution around flaws in capacitor materials have been modeled using the Finite Element and Finite Different methods respectively. This paper reviews the work done at The Pennsylvania State University on these two models.
Social support and verbal interaction are differentially associated with cognitive function in midlife and older age

ABSTRACTSocial engagement is associated with healthy aging and preserved cognition. Two dimensions of engagement, verbal interactions and perceived support, likely impact cognition via distinct mechanistic pathways. We explored the cognitive benefit of each construct among enrollees (N = 1,052, mean age = 60.2 years) in the Wisconsin Registry for Alzheimer’s Prevention study, who provide neuropsychological and sociobehavioral data at two-year intervals. Outcomes included six cognitive factor scores representing key domains of executive function and memory. Key predictors included self-reported perceived social support and weekly verbal interaction. Results indicated that after adjusting for lifestyle covariates, social support was positively associated with Speed and Flexibility and that verbal interactions were associated with Verbal Learning and Memory. These findings suggest that support, which may buffer stress, and verbal interaction, an accessible, aging-friendly form of environmental enrichment, ar...
Active Coping and Perceived Social Support Mediate the Relationship Between Physical Health and Resilience in Liver Transplant Candidates

Without a transplant, end-stage liver disease is associated with significant morbidity and mortality. Transplant candidates endure physical and psychological stress while awaiting surgery, yet little is known about the relationship between physical health and psychological resilience during the wait-list period. This study examined predictors of psychological resilience and mediators of the relationship between physical health and psychological resilience in liver transplant candidates. Wait-listed candidates (N = 120) from a single Northeast transplant center completed assessments of physical functioning, coping, perceived social support, and resilience. Findings revealed that physical functioning, active coping, and perceived social support were positively associated with resilience; maladaptive coping was negatively associated with resilience. Perceived social support and active coping partially mediated the relationship between physical functioning and resilience. Transplant center care providers should promote active coping skills and reinforce the importance of effective social support networks. These interventions could increase psychological resilience among liver transplant candidates.
“Occupying” the Internet: State media and the reinvention of official culture online:

The second decade of the new millennium in China has witnessed official media’s high-profile endeavors to “occupy” online sphere. Existing scholarship has examined, for instance, how the government at both the central and local levels assumes an increasingly proactive role in experimenting with new modes of e-governance. However, little critical attention has been paid to the reinvention of official culture that aims at having a stronger voice online, already a dynamic space occupied by numerous players competing for user attention and market share. This article fills this gap in literature and engages in a close reading of the Leon Dai incident in 2016. A renowned Taiwanese actor and director, Leon Dai’s role in Zhao Wei’s film No Other Love was replaced on July 15, 2016 because of his alleged ideological support of Taiwanese independence. The state media, as represented by the Weibo account of the Communist Youth League of China, played a crucial role in arousing nationalistic sentiments among Internet ...
Islet Microvasculature Alterations With Loss of Beta-cells in Patients With Type 1 Diabetes:

Islet microvasculature provides key architectural and functional roles, yet the morphological features of islets from patients with type 1 diabetes are poorly defined. We examined islet and exocrine microvasculature networks by multiplex immunofluorescence imaging of pancreases from organ donors with and without type 1 diabetes (n=17 and n=16, respectively) and determined vessel diameter, density, and area. We also analyzed these variables in insulin-positive and insulin-negative islets of 7 type 1 diabetes donors. Control islet vessel diameter was significantly larger (7.6 ± 1.1 μm) compared with vessels in diabetic islets (6.2 ± 0.8 μm; p<0.001). Control islet vessel density (number/islet) was significantly lower (5.3 ± 0.6) versus diabetic islets (9.3 ± 0.2; p<0.001). Exocrine vessel variables were not significantly different between groups. Islets with residual beta-cells were comparable to control islets for both vessel diameter and density and were significantly different from insulin-negative islets within diabetic donors (p<0.05). Islet smooth muscle actin area had a significant positive correlation with age in both groups (p<0.05), which could negatively impact islet transplantation efficiency from older donors. These data underscore the critical relationship of islet beta-cells and islet vessel morphology in type 1 diabetes. These studies provide new knowledge of the islet microvasculature in diabetes and aging.
Should There Be a Three-Strikes Rule against Pure Discovery Learning?.

The author's thesis is that there is sufficient research evidence to make any reasonable person skeptical about the benefits of discovery learning--practiced under the guise of cognitive constructivism or social constructivism--as a preferred instructional method. The author reviews research on discovery of problem-solving rules culminating in the 1960s, discovery of conservation strategies culminating in the 1970s, and discovery of LOGO programming strategies culminating in the 1980s. In each case, guided discovery was more effective than pure discovery in helping students learn and transfer. Overall, the constructivist view of learning may be best supported by methods of instruction that involve cognitive activity rather than behavioral activity, instructional guidance rather than pure discovery, and curricular focus rather than unstructured exploration.
Patient and family caregiver perspectives.

The introduction of any new analgesic agent or delivery system is often focused on efficacy of the agent or on considerations of use by health care professionals. Introduction of novel pain technologies should also consider the
Lasers, Microneedling, and Platelet-Rich Plasma for Skin Rejuvenation and Repair.

Skin resurfacing for the purpose of rejuvenation and repair continues to evolve with the development of noninvasive or minimally invasive surgical substitutes. Advances in laser therapy, microneedling, and platelet-rich plasma have reinvigorated research in wound repair and regenerative science. An overall positive clinical response toward the use of platelet-rich plasma as an adjuvant to fractional photothermolysis and percutaneous collagen induction is observed. Its effect on post-treatment adverse symptoms, erythema, edema, crusting, and clinical outcomes in rejuvenation are summarized in this article. The lack of identifiable complications and convenience of treatment provides a positive outlook for future use and investigations.
Rat kappa-chain allotypes

The distribution of rat kappa-chain allotype specificities (RI-1a and 1b) was studied amongRattus rattus and a variety of other Asian rodents. No sera other than those ofRattus norvegicus showed the presence of RI-1a (DA type), whereas many cross-reacted with RI-1b (LEW-type). While manyR. rattus showedtotal cross-reactivity with RI-1b, various sera from the generaRattus, Bandicota, andTokudaia showed different levels ofpartial cross-reactivity. These results indicate that (1) anti-RI-1b reagents can detectmultiple specificities on LEW-type kappa chains, and (2) these RI-1b specificities, butnot RI-1a, are widely distributed among murid rodents, in seeming contradiction to amino acid sequence data suggesting that RI-1b is more closely related to ancestral rat kappa chains.
A Software Defined Network Design for Analyzing Streaming Data in Transit

Year after year, network traffic keeps reaching new highs as unprecedented volumes of data flow between an ever-increasing number of sources and destinations. As part of the Analysis on the Wire project, we aim to develop a network-centric approach for streaming data processing to facilitate scientific data analysis and reduce the overhead in sending big data to a data center. This work discusses our design for programmable network devices to augment network capabilities for streaming data processing, including efforts in progress at Brookhaven National Laboratory and the challenges faced to date.
Time to thrombectomy is associated with increased risk for dialysis catheter placement.

Background Arteriovenous dialysis access, fistulae (AVF) or grafts (AVG), are associated with significant rates of thrombosis. Timely thrombectomy may have a significant impact on immediate and long-term access survival. However, switching to a catheter is associated with higher rates of morbidity and mortality compared with those who have an AVF or AVG. Objectives The goal of this study was to evaluate whether time to thrombectomy increases the risk for loss of dialysis access and subsequent placement of a dialysis catheter at hospital discharge, at 6 months, 12 months, and data at any time after discharge. Methods Using retrospective data, 444 patients were identified as having undergone thrombectomy for dialysis access dysfunction between January 2008 and April 2015, with 122 hospital admissions primarily for thrombectomy. Results The mean age was 60.4 years, 65% were male, and 44.3% had an arteriovenous fistula as their dialysis access. The mean time to thrombectomy was 10.8 hours, and 14 patients utilised a catheter for haemodialysis as primary access upon discharge. After adjustment for prior access intervention, access type, and time to thrombectomy, the adjusted odds ratios (AOR) of a one-day delay in thrombectomy was associated with a twofold increase in requirement for catheter at discharge and at 6 months. This association remained present at any time after discharge. Conclusion In this study of patients cared for within an academic health system, a single day delay in thrombectomy nearly doubled the risk of needing a dialysis catheter at hospital discharge, 6 months, or any time after discharge.
Tumor Sequencing: Enabling Personalized Targeted Treatments with Informatics

In recent years Next-Generation Sequencing (NGS)_ technology has provided expensive insights about the DNA structural and functional aberrations in multiple cancer types. These developments have been used to improvise diagnosis, prognosis, treatment discovery and personalizing treatments. This chapter reviews and highlights major informatics methods and initiatives, including in the area of assembling and sharing large clinico-genomic data sets for research and clinical care support.
Lendatus, a new genus of Xanthopygina (Coleoptera: Staphylinidae: Staphylininae) with description of three new species

A new genus of Xanthopygina rove beetles is described here as Lendatusgen. nov. The new genus includes three new species: L. bolivianussp. nov., described from Bolivia, L. philothalpiformissp. nov. described from Costa Rica and Panama, and L. platyssp. nov. described from Bolivia, Colombia, Ecuador and Peru. Lendatus belongs to the Isanopus group of genera of Xanthopygina and can distinguished from all the genera based on the unique punctation on the pronotum and the long apical setae of the paramere. A key to the three species of Lendatus along with photographs and illustrations is provided for the identification of species.
A Factor in Lungs of Anaphylactically Shocked Guinea Pigs Which Can Induce Eosinophilia in Normal Animals

1 . Absolute eosinophil counts of normal guinea pigs were obtained before, and twenty-four hours after, intraperitoneal implantation of lung slices from normal and sensitized guinea pigs, and of lung and other tissues—intestines, uterus, gall bladder, liver, and skin—from guinea pigs which died in anaphylactic shock. Changes in the number of circulating eosinophils of normal recipients were also determined after transfer of lung obtained from the same sensitized donor animal before and after reinjection of the specific antigen, and of lungs from shocked animals incubated at 56 C. for 40 minutes. 2. Transfer of lung tissue from normal and sensitized (but not reinjected) guinea pigs into the peritoneal cavity of normal animals produces a significant, but limited, increase in the number of circulating eosinophils of the recipients. 3. Transfer of lung tissue of guinea pigs which died in anaphylactic shock into the peritoneal cavity of normal recipients produces a marked transitory eosinophilia. 4. Removal and transfer of one lung of sensitized guinea pigs, compared with transfer of the other lung after reinjection of the specific antigen demonstrates that the eosinotactic factor develops immediately after anaphylactic shock. 5. Transfer of intestines, uterus, gall bladder, and liver (compared with lung) of shocked guinea pigs into the peritoneal cavity of normal animals produces a small, but significant, transitory increase in the number of circulating eosinophils in the recipient; transfer of skin in a limited number of experiments appears to depress the peripheral eosinophil count of the recipients. 6. Transfer of lung tissue from shocked donors incubated at 58 C. for 40 minutes produces a less marked eosinophilia in normal recipients than transfer of lung tissue kept at room temperature for the same period.
Adaptation of a Mental Health Treatment Engagement Intervention for Older Foster Youth

Youth who exit foster care often have mental health treatment histories, but they commonly discontinue treatment after exiting the system. The purpose of this study was to adapt an intervention designed to improve engagement/investment in mental health treatment, specifically to be delivered to youth aging out of foster care. An iterative process that incorporated focus groups with both youth and providers was used to adapt the original intervention curriculum, then the feasibility of implementation of the adapted intervention in settings for older foster youth was explored. Language of the intervention manuals was modified so terms resonated more with youth and was simplified to be accessible to low reading levels. Two new sessions were added to provide skills for talking with providers and to assist in incorporating mental health into broader transition goals for foster youth. The adapted intervention was implemented on an ongoing basis at a transition drop-in center. The adapted intervention was found to be acceptable by facilitators and youth participants. The most feasible and acceptable content and setting for the group to be implemented in an ongoing way emerged from the results. Future efficacy studies are needed to determine whether outcomes such as attitudes toward mental health services and engagement are changed by the intervention. Preliminary testing supports the potential for integrating the adapted engagement intervention into broader transition planning efforts since mental health has strong connections with other transition domains.
Evidence of an Inherited Predisposition for Spinal Cord Tumors.

Study Design:Retrospective study.Objectives:To determine familial clustering of primary spinal cord tumors using a statewide genealogy database.Methods:The Utah Population Database (UPDB) was queri...
Carving depression at its joints? Psychometric properties of the Sydney Melancholia Prototype Index

Parker and colleagues developed the Sydney Melancholia Prototype Index (SMPI), a 24-item measure to assess a potential subtype of depression: melancholia. While research supports the validity of the measure, no study has assessed its psychometric properties. We recruited 1633 participants online, of whom 487 reported a lifetime period of depressed mood or anhedonia and were administered the SMPI. We conducted confirmatory factor analyses (CFA) of the SMPI, to assess the proposed fit of the measure. We also conducted exploratory factor analyses (EFA) to explore the structure implied by the current data. CFA did not support the hypothesized factor structure of the SMPI, no matter what structure we assumed as primary (i.e., a one factor, two factor, or bifactor model). An EFA suggested a five-factor solution wherein several items did not appear to co-vary reliably and other factors captured the severity of melancholic symptoms, negative mood reactivity, positive mood reactivity, emotionality and family relationships, and early life adversity. The SMPI may not measure a single construct. Future research should explore the longitudinal association between depression severity, contaminant symptoms, positive and negative mood reactivity, and early life experiences.
Sample size determination for Bayesian analysis of small n sequential, multiple assignment, randomized trials (snSMARTs) with three agents.

The small n, Sequential, Multiple Assignment, Randomized Trial (snSMART) is a two-stage clinical trial design for rare diseases motivated by the comparison of three active treatments for isolated s...
Feasibility Trial of an eHealth Intervention for Health-Related Quality of Life: Implications for Managing Patients with Chronic Pain during the COVID-19 Pandemic

Purpose: This study was conducted to determine the feasibility of providing an eHealth intervention for health-related quality of life (HRQOL) to facilitate patient self-management. Methods: A randomized controlled trial was conducted from 2019–2020 within the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation. Eligible patients included those with chronic low back pain and a SPADE (sleep disturbance, pain interference with activities, anxiety, depression, and low energy/fatigue) cluster score ≥ 55 based on the relevant scales from the Patient-Reported Outcomes Measurement Information System instrument with 29 items (PROMIS-29). Patients were randomized to the eHealth treatment group, which received a tailored HRQOL report and interpretation guide, or to a wait-list control group. The primary outcome was change in the SPADE cluster score, including its five component scales, over 3 months. Secondary outcomes were changes in low back pain intensity and back-related disability. Treatment effects were measured using the standardized mean difference (SMD) in change scores between groups. The eHealth intervention was also assessed by a survey of the experimental treatment group 1 month following randomization. Results: A total of 102 patients were randomized, including 52 in the eHealth treatment group and 50 in the wait-list control group, and 100 (98%) completed the trial. A majority of patients agreed that the HRQOL report was easy to understand (86%), provided new information (79%), and took actions to read or learn more about self-management approaches to improve their HRQOL (77%). Although the eHealth intervention met the criteria for a small treatment effect in improving the overall SPADE cluster score (SMD = 0.24; p= 0.23) and anxiety (SMD = 0.24; p = 0.23), and for a small-to-medium treatment effect in improving depression (SMD = 0.37; p = 0.06) and back-related disability (SMD = 0.36; p = 0.07), none of these results achieved statistical significance because of limited sample size. Conclusion: Given the feasibility of rapid online deployment, low cost, and low risk of adverse events, this eHealth intervention for HRQOL may be useful for patients with chronic pain during the COVID-19 pandemic.
BLOOD TRANSFUSION FOR PATIENTS IN PAEDIATRIC INTENSIVE CARE UNITS: ARE WE COMPLYING WITH THE GUIDELINES?

Objective A new formula has been recommended to standardise the calculation of the volume required for blood transfusion across all age and diagnostic groups of patients in paediatric intensive care units (PICU). The application of the new formula was audited against clinical practice in the PICU in Birmingham Children’s Hospital, UK. Volume of packed cell (ml) = 4.8 × weight (kg) × desired rise in haemoglobin (g/dl) (Morris 2005, Davies 2007). Methods A comparison of the actual volume of blood transfused and the “ideal” volume of blood calculated from the new formula was documented in critically ill children. Confounding factors, eg, active bleeding, haemolysis, recent surgery and cyanotic heart disease, were taken into account. Results Transfusion volumes were documented for 28 children (median age 16 days, range 3 days to 5 years) over 8 weeks. The correct volume (±10%) was transfused in 19 children. Five patients (18%) were over-transfused (factor of 6.3−7.5×). None of these patients had active bleeding or haemolysis. Four patients (14%) were under-transfused (factor 3.3−4.0×). Two of the patients that were under-transfused required a further blood transfusion within 3 days. Conclusions The application of this new formula is not being widely used in clinical practice. The implementation of this formula could be improved by the introduction of electronic blood product prescribing and more widespread and purposeful education. An accurate calculation of volume required for paediatric patients could reduce multiple transfusions, reducing risks and cutting costs.
Agrochemical Exposure & Environmental Illness: Legal Repression of Latin American Banana Workers

Prior research on legal repression shows how elites use criminal law to demobilize collective challenges, yet social control efforts based in civil law have received inadequate attention. In this s...
The Intriguing Clinical Success of BCL-2 Inhibition in Acute Myeloid Leukemia

Over the past several decades numerous preclinical and clinical studies have pursued new approaches for the treatment of acute myeloid leukemia (AML). While some degree of clinical response has bee...
Mastitis Control in Replacement Heifers

Mastitis is the most costly disease of dairy cattle. This disease occurs when bacteria penetrate the teat orifice, colonize teat canal keratin, and gain entry into the mammary gland. In spite of growth inhibitory properties of keratin bacteria are able to survive in the teat canal and progress into the udder, causing inflammation. Current methods of mastitis control advocate adoption of management practices developed for mature lactating and dry cows, and include teat dipping, dry cow therapy, proper use of functionally adequate milking machines, prompt treatment of clinical cases, and culling of chronically infected animals. However, methods for controlling the disease in heifers were not contemplated in development of these management schemes. Mammary glands of heifers have traditionally been regarded as uninfected, and their mammary secretions are not examined until the first milking or during the first episode of clinical mastitis following calving. The greatest development of milk producing tissue in heifers occurs during the first pregnancy, thus mammary glands must be protected from the harmful effects of mastitis-causing bacteria to insure maximum milk production and reduce the level of infection and somatic cell count (SCC) during the subsequent lactation. This is particularly important in view of the recent decision to lower the SCC legal limit. Effective July, 1993, the new Interstate Milk Shippers' quality standard for raw milk will set the SCC limit at 750,000/ml. Thus, in addition to tightening up standard mastitis control practices in lactating and dry cows, dairymen should carefully consider a mastitis control program for heifers in attempts to conform to the new quality standard.
Severe aortic stenosis is associated with perioperative mortality in proximal femur fracture patients.

Objectives Evaluate the correlation between aortic stenosis and perioperative mortality in patients following surgical fixation of proximal femur fractures. Design Retrospectively reviewed case series. Setting Two Academic, Level 1 Trauma Centers. Patients/participants One hundred fifty-eight patients, definitively diagnosed with aortic stenosis by means of echocardiogram, who underwent surgical fixation for an isolated proximal femur fracture (OTA/AO 31-A, 31-B, 32-A, 32-B, and 32-C fractures) between January 2000 and June 2015. The severity of the aortic stenosis was based upon accepted echocardiographic hemodynamic parameters designated by the 2014 American Heart Association guidelines. Main outcome measures Post Injury mortality, 30-day mortality, and 1-year mortality. Secondary outcome measures Postoperative mortality stratified by severity of aortic stenosis based on aortic valve area (AVA) and ejection fracture (EF) as determined by preoperative echocardiography. Results One hundred fifty-eight patients were available for final analysis. Kaplan-Meier survival analysis revealed a significantly longer time to mortality among Non-severe aortic stenosis patients compared to Severe aortic stenosis patients, P value .006. Twenty-three percent of patients with Severe aortic stenosis and 10% of patients with Non-severe aortic stenosis died within 30 days of surgery. No significant difference was observed in mean survival among AS patients who underwent surgery within 48 hours of injury (34.5 months) and those delayed more than 48 hours after injury (25.0 months), P value .116. Among the commonly measured hemodynamic parameters of aortic stenosis, only AVA and EF were significantly associated with mortality, P value .015, and P value 0.8 cm2. (37 months), P value .009. Conclusions Severe aortic stenosis is associated with a shorter postoperative time to mortality after surgical fixation of hip fractures compared to patients with Non-severe stenosis. Aortic valve area and Ejection Fraction are the only hemodynamic parameters significantly associated with postoperative mortality.Level of Evidence: Prognostic Level III.
Forming syncytia by vegetative cell fusions in the coralline red alga Neopolyporolithon reclinatum (Rhodophyta, Hapalidiales)

Light microscopy and transmission electron microscopy were used to examine the developmentally important but little studied process of red algal vegetative cell fusion. Cell fusions were pervasive ...
Functional intersections between extracellular vesicles and oncolytic therapies

Minimally invasive focal therapies for nonviral oncolysis are a cornerstone of cancer therapeutics. Our ability to optimally deploy oncolytic therapies and identify synergistic combination approaches requires a deeper understanding of elicited biological responses. Extracellular vesicles (EV), which orchestrate a variety of pathophysiological processes and have a critical role in the evolution of primary and disseminated tumors, are now known to be potently modulated by oncolytic focal therapies, such as radiotherapy, photodynamic therapy (PDT), and therapeutic ultrasound (TUS). In this review, we summarize the diverse impacts of the aforementioned therapeutic modalities on EV biology, and highlight the most recent advances in EV-based drug delivery systems leveraging these modalities.
Mobile phone based mini-spectrometer for rapid screening of skin cancer

We demonstrate a highly sensitive mobile phone based spectrometer that has potential to detect cancerous skin lesions in a rapid, non-invasive manner. Earlier reports of low cost spectrometers utilize the camera of the mobile phone to image the field after moving through a diffraction grating. These approaches are inherently limited by the closed nature of mobile phone image sensors and built in optical elements. The system presented uses a novel integrated grating and sensor that is compact, accurate and calibrated. Resolutions of about 10 nm can be achieved. Additionally, UV and visible LED excitation sources are built into the device. Data collection and analysis is simplified using the wireless interfaces and logical control on the smart phone. Furthermore, by utilizing an external sensor, the mobile phone camera can be used in conjunction with spectral measurements. We are exploring ways to use this device to measure endogenous fluorescence of skin in order to distinguish cancerous from non-cancerous lesions with a mobile phone based dermatoscope.
The Deciduous Forest - Boreal Forest Ecotone: Deciduous - boreal forest ecotone

Ecotones have been subject to significant attention over the past 25 years as a consensus emerged that they might be uniquely sensitive to the effects of climate change. Most ecotone field studies and modeling efforts have focused on transitions between forest and non-forest biomes (e.g. boreal forest to Arctic tundra, forest to prairie, subalpine forests to alpine tundra) while little effort has been made to evaluate or simply understand forest–forest ecotones, specifically the deciduous forest – boreal forest ecotone. Geographical shifts and changes at this ecotone because of anthropogenic factors are tied to the broader survival of both the boreal and deciduous forest communities as well as global factors such as biodiversity loss and dynamics of the carbon cycle. This review summarizes what is known about the location, controlling mechanisms, disturbance regimes, anthropogenic impacts, and sensitivity to climate change of the deciduous forest – boreal forest ecotone.
Number of automorphisms

This cardinal function is not related very much to the preceding ones. To start with, we state some general facts about the size of automorphism groups in BAs; for proofs or references, see the chapter on automorphism groups in the BA handbook.
Verification Simulation Acceleration UsingCode-Perturbation

We propose a simulation approach that can take a large design and swiftly cover its valid code-level operating states. The approach perturbs the program-control flow during the simulation to dynamically exhaust all branching possibilities in a verification code/program. The heuristic uses the program branching information from preprocessing the test/verification code. Using the branching information the simulation allows automatic run-time forced branching to make possible a full coverage of the instruction space spanned by the verification code/program. The aim is (1) to improve the verification simulation speed and (2) to get higher coverage rate for large core-base designs such as microprocessors or digital-signal-processing (DSP) products. A case study of a 32-bit RISC processor, used in a network system, is conducted. The application code for the processor (MCP, Myrinet control program) is used as a verification program. Despite the deviation from the valid “software-reachable state” of the system due to forced branching, a significant number of hard-to-reach hardware states (that can be reached only through the right mix of codes, often the code segments of an application software) are covered. Using the MCP program over 30% additional coverage is achieved with the proposed approach over ordinary code-based simulation for a fixed verification time. Further, compared to the conventional simulation approach, the proposed heuristic takes about 43% less compute-cycles to achieve same state coverage level.
Hormonal regulation of spermatogenesis in the hypophysectomized rat: cell viability after hormonal replacement in adults after intermediate periods of hypophysectomy

A quantitative analysis of germ-cell populations in normal, hypophysectomized (Hx), and Hx-hormone-treated animals was undertaken during periods of regression that were characterized as intermediate, between short-term and long-term regression of the testis. Twenty-one groups of adult rats were administered either follicle-stimulating hormone (FSH), growth hormone, thyroid-stimulating hormone (TSH), or testosterone (T) in various doses and combinations. The dosage of T administered was less than that expected to achieve maximum testis weight. Flutamide and Casodex were used to compete with androgen binding to receptors in Hx animals, as it is known that small amounts of androgen are secreted in the absence of pituitary stimulation. Follicle-stimulating hormone, T, and TSH all significantly maintained testis weight as compared with Hx controls, although FSH and T, singly or in combination, were the most effective. Contamination of the TSH preparation with trace amounts of FSH was apparently responsible for the slight maintenance of testis weight. A novel assay for determination of the numbers of viable germ cells was used in a subset of these groups to determine the cellular sites of FSH and T action. Numbers of type A spermatogonia were lowered after Hx and were maintained by either FSH or T or a combination of these hormones. Other phases of germ-cell development most susceptible to FSH and/or T were the successive conversions of type A spermatogonia to intermediate spermatogonia, intermediate spermatogonia to type B spermatogonia, preleptotene spermatocytes to pachytene spermatocytes, and early pachytene spermatocytes to intermediate maturity pachytene spermatocytes during early and midcycle phases of pachytene spermatocyte development. Germ-cell loss during meiosis and virtually every phase of spermatid development was largely prevented by FSH or T or a combination of these hormones. Thus, in testes in advanced stages of regression, both FSH and T were capable of preventing cell loss, suggesting that both hormones can affect the survival of the same cell type. The present study demonstrated that FSH can partially compensate for lowered T levels. The combined administration of FSH and T was more effective in preventing overall cell degeneration than either hormone alone. Unlike the initial phase of spermatogenesis, in which there is a largely midcycle loss of germ cells due to Hx, the loss of cells during testis regression is more widespread and impacts several cell types in more than one stage of the spermatogenic cycle.
A comparative study of dynamically expanding force-free, constant-alpha magnetic configurations with applications to magnetic clouds

We contrast two different solutions of the constant alpha, force-free MHD equation, both of which have been suggested as models for magnetic clouds: a solution in cylindrical coordinates and one in spherical coordinates. In line with the observation that magnetic clouds expand, we generalize these static models and construct their expanding counterparts. We find that expansion introduces in both cases a large asymmetry in the field strength signature which is in the same sense as that seen the the data, i.e. towards the leading edge of the cloud. We then do a least squares fit of the respective models to one-spacecraft data on a magnetic cloud. We find that the fitting routine converges in both cases. However, while purely formally we cannot distinguish between the two models using data from one spacecraft, the field components in the 'spherical' model have features not compatible with data on magnetic clouds.
Physical Aggregation and Functional Reconstitution of Solubilized Membranes of Bacillus stearothermophilus

Isolated membranes of Bacillus stearothermophilus 2184D can be disrupted by treatment with sodium dodecyl sulfate (SDS). This disruption is attended by a decreased turbidity of membrane suspensions and a differential loss of activities of the electron transport system. Reduced methyl viologen (MVH)-nitrate reductase activity is insensitive to SDS treatment, whereas reduced nicotinamide adenine dinucleotide (NADH)-nitrate reductase and cyanide-sensitive NADH oxidase activities are decreased by 80% at an SDS concentration of 0.5 mg/mg of membrane protein. NADH-menadione reductase activity is unaffected at this SDS concentration, but at higher detergent levels it also decreases in activity. The abilities of NADH to reduce and nitrate to oxidize the cytochrome components of the membrane were also decreased after SDS treatment. Dilution of solubilized membrane in buffer containing divalent cation results in formation of an aggregate with an increased turbidity and reconstituted NADH-nitrate reductase and cyanide-sensitive NADH oxidase activities. Of several cations tested, magnesium was the most effective, and the reconstitution process was pH-dependent with an optimum at pH 7.4. Intact and aggregated membranes had similar densities and cytochrome contents, and the sensitivity of NADH-nitrate reductase to several inhibitors was similar in intact and reconstituted membranes.
Unequal channel spacings to reduce four-wave mixing crosstalk in WDM networks

Four-wave mixing (FWM) is the most serious fiber nonlinearity in long-haul multichannel optical systems employing dispersion-shifted fiber. To reduce the crosstalk due to FWM, a general suboptimum unequally spaced channel allocation technique is proposed and analyzed.
Development and prognosis of histologic cirrhosis in corticosteroid-treated hepatitis B surface antigen-negative chronic active hepatitis

Abstract To determine the frequency and prognosis of histologic cirrhosis developing during or after corticosteroid therapy of hepatitis B surface antigen-negative chronic active hepatitis, we followed 83 patients for 90 ± 5 mo after administration of corticosteroids. Thirty-three patients satisfied histologic criteria for cirrhosis after 30 ± 5 mo. In 25 patients, cirrhosis developed during treatment; in 8 patients, cirrhosis eventuated after remission and cessation of therapy. The probability of developing histologic findings of cirrhosis was 59% if remission had not been achieved after 3 yr of continuous therapy. Longer requirements for treatment and deterioration during therapy characterized these patients. Once remission was achieved, the mean annual incidence of cirrhosis was only 2.6%. Patients who manifested evidence of cirrhosis in their biopsy specimens could not be distinguished by initial clinical, biochemical, or histologic findings. Ascites, encephalopathy, and esophageal varices developed infrequently; 5-yr survival after documentation of cirrhosis was 93%. We conclude that histologic features of cirrhosis develop commonly during therapy, especially if remission is not achieved quickly. After remission, cirrhosis develops infrequently. The development of histologic cirrhosis does not influence immediate morbidity and 5-yr life expectancy.
Exercise-induced growth in golden hamsters: Effects of age, weight, and activity level

Abstract The relationship between the exercise-induced growth and the endogenous controls of growth was examined in 356 golden hamsters of which equal numbers were given access to horizontal disc exercisers and maintained sedentary at different ages (17 and 42 days) and body weights (25–180 g). Hamsters started exercising around Day 35, increased their activity levels to 30,000 revolutions per day (RPD) by Day 35, and ran progressively less as their weight increased above 65 g. Exercise accelerated growth only in hamsters which have entered the slow asymptotic phase of growth, which weighed between 60–180 g and generated over 15,000 RPD. Disc exercise appears to reinstate higher rates of ponderal and linear growth after hamsters have entered the slow asymptotic phase of growth. Sustained inhibition of exponential growth may participate in the long-term regulation of body size in adult rodents.
The big picture on nanomedicine: the state of investigational and approved nanomedicine products

Developments in nanomedicine are expected to provide solutions to many of modern medicine's unsolved problems, so it is no surprise that the literature contains many articles discussing the subject. However, existing reviews tend to focus on specific sectors of nanomedicine or to take a very forward-looking stance and fail to provide a complete perspective on the current landscape. This article provides a more comprehensive and contemporary inventory of nanomedicine products. A keyword search of literature, clinical trial registries, and the Web yielded 247 nanomedicine products that are approved or in various stages of clinical study. Specific information on each was gathered, so the overall field could be described based on various dimensions, including FDA classification, approval status, nanoscale size, treated condition, nanostructure, and others. In addition to documenting the many nanomedicine products already in use in humans, this study indentifies several interesting trends forecasting the future of nanomedicine.
Aging and Repeated Thought Suppression Success

Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults’ thought suppression outcomes changed over time, while trajectories for older adults’ were relatively stable. Results are discussed in terms of older adults’ reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility.
Sensitivity analysis of materials availability for terawatt PV deployment

The road map for cost competitive large-scale PV deployment is ever changing and with PV grade poly silicon prices averaging 16 U$D/kg and companies focusing on using less materials the cost effectiveness of readily available materials for solar cell applications should be revisited. In this work we analyze to which extent the extraction cost of the absorber layer material plays a role in the overall cost of generating electricity, taking into account the potential for light trapping and the non-power producing component costs. Our calculations show that nearly all presently used materials have fundamental cost and availability potential which are well below a level at which material availability is a dominant consideration. Instead, constraints on parameters such as the amount of copper for wiring or substrate material for module fabrication become dominant issues.