cssi/SciSciGPT-SciSciNet huggingface dataset:
633. A Reproducible and Reliable Non-Invasive Approach to Assess the Efficacy of Gene Therapy in mdx Mice with Relevance to Clinical Trials

The mdx mouse carries a naturally occurring nonsense mutation in the dystrophin gene and has become a critical animal model for research on Duchenne Muscular Dystrophy (DMD). Despite the extensive published studies on muscle structure and function in this model, we still lack appropriate protocols for evaluation of functional rescue in mdx mice using non-invasive tests relevant to the clinically relevant symptoms of DMD. Here we present for the first time results of a complex approach for the evaluation of locomotor and behavioral patterns of mdx mice during running wheel performance in a modified open field monitoring system. These results are examined in the same mice with force grip measurements and serum enzyme biomarker creatine kinase (CK) measurement. The comparison between juvenile congenic wild type (C57Bl10) and mdx mice indicates similarity in parameters such as rest time and the number of times entering and initiating use of the running wheel per day, but highly significant differences with regard to running wheel-associated locomotor activity characteristics including velocity, time, distance per run, and total distance per day. This suggests that exploratory behavior at low work rate is unaffected by dystrophin deficiency, but that the animals respond to as yet uncharacterized sensory inputs that limit their running speed and duration without preventing the desire to re-initiate after rest. This may be viewed as analogous to the early loss of function and metabolic reserve in the juvenile period of DMD disease progression, where boys are described by parents as frustrated at first being unable to keep pace with their friends. As presented in another poster by our group, blinded studies of the response to gene therapy indicates that it is unlikely that this phenotypic difference reflects the mislocalization of neuronal nitric oxide synthase (nNOS) in dystrophin deficiency. In further blinded studies, the open field data correlate with the differences in testing results between the two mouse strains observed in the force grip evaluation and serum levels of CK, offering possible leads for a further mechanistic dissection. These results demonstrate strong evidence in support of the running wheel open field system as a reliable and reproducible approach to assess the therapeutic efficacy in the mouse model of DMD. This approach also provides a platform for dissecting the physiological roles of dystrophin in supporting precisely measurable volitional activities in unrestricted animals, thereby offering potential improvements in the predictive power of preclinical studies of therapeutic efficacy to inform clinical trials.
Validation and application of a forest gap model to the southern Rocky Mountains

Abstract Rocky Mountain forests are highly important for their part in carbon cycling and carbon storage as well as ecosystem services such as water retention and storage and recreational values. These forests are shaped by complex interactions among vegetation, climate, and disturbances. Thus, climate change and shifting disturbances may lead to significant changes in species composition and biomass. Individual tree-based modeling allows various climate change scenarios and their effects on forest dynamics to be tested. We use an updated individual-based gap model, the University of Virginia Forest Model Enhanced (UVAFME) at four sites in the southern Rocky Mountains. UVAFME is quantitatively and qualitatively validated at these sites against inventory data and descriptions of vegetation zonation and successional dynamics. Results show that UVAFME can be used to reasonably simulate the expected change in species composition with elevation for the southern Rocky Mountains region. UVAFME output on size structure (stems size class−1 ha−1) and species-specific biomass (tonnes C ha−1) is comparable to forest inventory data at these locations. UVAFME can also simulate successional dynamics to accurately predict changes in species dominance with landscape age. We then perform a hypothetical climate sensitivity test in which temperature is first increased linearly by 2 °C over 100 years, stabilized for 200 years, cooled back to present climate values over 100 years, and again stabilized for 200 years. Results show that elevated temperatures within the southern Rocky Mountains may lead to decreases in biomass and shifts upslope in species composition, especially that of ponderosa pine (Pinus ponderosa), Douglas-fir (Pseudotsuga menziesii), and lodgepole pine (Pinus contorta). At some ecotones these changes are also likely to be fairly long lasting for at least 100 years. The results from these tests suggest that UVAFME and other individual-based gap models can be used to inform forest management and climate mitigation strategies for this region.
In-Die Through-BEOL Metal Wall for Noise Isolation in 180-nm FD-SOI CMOS

This letter reports a conceptual in-die through-back-end-of-the-line metal wall structure for noise isolation demonstrated in a foundry 180-nm fully depleted silicon-on-insulator (FD-SOI) CMOS technology. The near-closed-loop isolation wall was made of a trench ring etched by focused ion beam and filled with silver nano powder in a post-CMOS process module developed. Crosstalk suppression was confirmed in measurement that shows a reduction of around 9 dBm in the third-order intermodulation interferers as predicted full-wave electromagnetic co-simulation. The structure can be readily integrated into the foundry technologies as a potential crosstalk reduction solution for mixed-signal integrated circuits in FD-SOI CMOS processes.
Fund of Funds Selection of Mutual Funds Superior Knowledge versus Family and Management Goals

Managers of Fund of Funds have access to information not available to the general public in evaluating funds from their own family. However, they may have family or self‐serving motives that can hurt shareholder performance. By examining a history of individual transactions of Funds of Funds, we show that managers of Fund of Funds despite access to nonpublic information select individual funds that underperform random selection. Much of this underperformance is shown to be explained by managers satisfying a specific set of family and management goals. Fund of Funds that invest exclusively outside their fund family do not face these family and management goals and they outperform funds of funds then invest inside the family.
Abstract 084: Sodium Butyrate and Retinoic Acid Attenuate Renal Inflammation and Fibrosis in Npr1 Gene-targeted Haplotype Mice: Role of NF-κB Signaling

The objective of the present study was to determine the effect of a hybrid drug of sodium butyrate (NaBu), a histone deacetylase (HDAC) inhibitor and all-trans retinoic acid (ATRA) on the attenuation of renal inflammation and fibrosis in Npr1 gene-disrupted mutant mice. Adult (18-20 week old) male Npr1 gene-disrupted heterozygous (1-copy; Npr1 +/-) wild-type (2-copy; Npr1 +/+), and gene-duplicated (3-copy; Npr1 ++/+) mice were treated with ATRA-NaBu hybrid drug (1.0 mg/kg/day) by intraperitoneal injections for 2-weeks. A significant decrease in systolic blood pressure was observed in ATRA-NaBu-treated haplotype Npr1 +/- mice compared with untreated controls (treated, 113.3 ± 1.5 vs. control, 130.4 ± 1.9; p < 0.01). After treatment with ATRA-NaBu, a marked reduction in tubulo-interstitial fibrosis (50%, p < 0.001) and decreased renal collagen type I alpha 2 expression by 55% (treated, 25.9 ± 1.2 vs. control, 57.2 ± 2.9, p < 0.001) was observed in Npr1 +/- mice. Treatment with ATRA-NaBu also increased creatinine clearance (ml/24 h) in Npr1 +/- mice (245.7 ± 24.3 vs. control, 83.8 ± 3.9). Similarly, higher urinary albumin to creatinine ratio was detected in Npr1 +/- mice (0.84 ± 0.03) vs. control (0.35 ± 0.03; p < 0.01) and a complete reversal was observed in drug-treated Npr1 +/- mice (0.39 ± 0.05). Significant decreases were observed in renal (pg/mg protein) tumor necrosis factor-alpha (TNF-α) (4.1 ± 0.7 vs. control, 27.2 ± 2.6; p < 0.01) and interleukin (IL)-6 (11.8 ± 0.8 vs. control, 59.9 ± 3.6; p < 0.01) in ATRA-NaBu-treated Npr1 +/- mice. Western blot analyses showed significant reduction in renal TNF-α and IL-6 protein expression by 54%, (p < 0.001) and 61%, (p < 0.01), respectively, in ATRA-NaBu-treated Npr1 +/- mice. There was 49% increase in renal NF-κB (p65) DNA binding activity in Npr1 +/- mice and 51% lower activity in Npr1 +/++ mice compared with wild-type mice. Western blot analysis revealed distinctly higher levels of renal NF-κB (p65) protein expression in Npr1 +/- mice and reduced levels in Npr1 +/++ mice compared with wild-type controls. The present results provide direct evidence that ATRA-NaBu hybrid drug acts as a potent anti-inflammatory agent, which will have important implications in the pathophysiology of renal injury and hypertension.
A single-operator learning curve analysis for the endoscopic sleeve gastroplasty

Background and Aims Endoscopic sleeve gastroplasty (ESG) is a novel, incisionless technique for gastric volume reduction to promote weight loss. Our aim was to describe the learning curve for performing ESG using a prospective case series. Methods Using a prospective case series design, we analyzed the first 128 consecutive patients at a tertiary care academic medical center who underwent ESG performed by a single operator from August 2013 to December 2016. Efficiency (refining performance to decrease procedure time) and mastery (absence of outliers) for performing ESG was evaluated by using a penalized basis-spline regression and cumulative sum analysis. Results Efficiency for ESG was attained after 38 ESGs, with mastery after 55 procedures. At 12 months, the mean percent total body weight loss was 15.8% (standard deviation, 9.47%). A total of 71.7% of patients achieved successful weight loss. When using multiple linear regression analysis, both number of sutures and baseline weight were significantly associated with procedure time. Other patient characteristics, such as age, sex, and race, did not significantly affect procedure time. In addition, number of sutures, baseline weight, and endoscopist achieving efficiency were not correlated with successful weight loss at 12 months. Conclusions Mastery of ESG by a single operator is suggested after sufficient endoscopic experience and may help guide widespread clinical adaptability.
Control beliefs are associated with preserved memory function in the face of low hippocampal volume among diverse older adults

Growing evidence supports a link between locus of control and memory in older adults. Control beliefs may directly predict larger hippocampal volume (i.e., brain maintenance). Alternatively, control beliefs may be associated with smaller hippocampal volume at any given level of memory (i.e., cognitive reserve). Multivariable regression analyses examined associations between verbal episodic memory, locus of control and hippocampal volume among 236 non-demented older adults in the community-based Washington Heights-Inwood Columbia Aging Project. Control beliefs were negatively associated with hippocampal volume when controlling for memory performance, indicating that individuals with stronger control beliefs were able to maintain memory function in the face of lower hippocampal volume. Subsequent exploratory models stratified by race/ethnicity indicated that this association was more prominent among racial/ethnic minorities (particularly Caribbean Hispanic older adults) than among non-Hispanic White older adults. Control beliefs were not associated with hippocampal volume before memory was taken into account. Results are consistent with the view that control beliefs facilitate the maintenance of memory function despite hippocampal volume loss. Results are not consistent with the view that locus of control contributes to brain maintenance. Culturally-appropriate interventions are needed to test whether strengthening control beliefs provides cognitive resistance to neuropathology.
The effect of mixing on fermentation of primary solids, glycerol, and biodiesel waste

In this study, the effect of mixing on volatile fatty acid (VFA) production and composition was investigated through running five identical bench-scale reactors that were filled with primary solid and dosed with either pure glycerol or biodiesel waste. Experimental results revealed that there was an inverse correlation between the mixing intensity and the VFA production. The total VFA production in the un-mixed reactor was 9,787 ± 3,601 mg COD/L, whereas in the reactor mixed at 100 rpm this dropped to 3,927 ± 1,175 mg COD/L, while both types of reactor were dosed with pure glycerol at the beginning of each cycle to reach the initial concentration of 1,000 mg/L (1,217 mg COD/L). Propionic acid was the dominant VFA in all the reactors except the reactor mixed at 30 rpm. It is hypothesized that low mixing facilitated hydrogen transfer between obligate hydrogen producing acetogens (OHPA) and hydrogen consuming acidogens in these non-methanogenic reactors. Also, in a narrower range of mixing (0 or 7 rpm), the total VFA production in biodiesel waste-fed reactors was considerably higher than that of pure glycerol-fed reactors.
Generation of nanobubbles by ceramic membrane filters: The dependence of bubble size and zeta potential on surface coating, pore size and injected gas pressure.

Generation of gaseous nanobubbles (NBs) by simple, efficient, and scalable methods is critical for industrialization and applications of nanobubbles. Traditional generation methods mainly rely on hydrodynamic, acoustic, particle, and optical cavitation. These generation processes render issues such as high energy consumption, non-flexibility, and complexity. This research investigated the use of tubular ceramic nanofiltration membranes to generate NBs in water with air, nitrogen and oxygen gases. This system injects pressurized gases through a tubular ceramic membrane with nanopores to create NBs. The effects of membrane pores size, surface energy, and the injected gas pressures on the bubble size and zeta potential were examined. The results show that the gas injection pressure had considerable effects on the bubble size, zeta potential, pH, and dissolved oxygen of the produced NBs. For example, increasing the injection air pressure from 69 kPa to 414 kPa, the air bubble size was reduced from 600 to 340 nm respectively. Membrane pores size and surface energy also had significant effects on sizes and zeta potentials of NBs. The results presented here aim to fill out the gaps of fundamental knowledge about NBs and development of efficient generation methods.
Patterns in Health Care Access and Affordability Among Cancer Survivors During Implementation of the Affordable Care Act.

Importance Cancer survivors face ongoing health issues and need access to affordable health care, yet studies examining health care access and affordability in this population are lacking. Objectives To evaluate health care access and affordability in a national sample of cancer survivors compared with adults without cancer and to evaluate temporal trends during implementation of the Affordable Care Act. Design, Setting, and Participants We used data from the National Health Interview Survey from 2010 through 2016 to conduct a population-based study of 30 364 participants aged 18 years or older. We grouped participants as cancer survivors (n = 15 182) and those with no reported history of cancer, whom we refer to as control respondents (n = 15 182), matched on age. We excluded individuals reporting a cancer diagnosis prior to age 18 years and those with nonmelanoma skin cancers. Main Outcomes and Measures We compared issues with health care access (eg, delayed or forgone care) and affordability (eg, unable to afford medications or health care services) between cancer survivors and control respondents. We also explored trends over time in the proportion of cancer survivors reporting these difficulties. Results Of the 30 364 participants, 18 356 (57.4%) were women. The mean (SD) age was 63.5 (23.5) years. Cancer survivors were more likely to be insured (14 412 [94.8%] vs 13 978 [92.2%],P Conclusions and Relevance Despite higher rates of insurance coverage, cancer survivors reported greater difficulties accessing and affording health care compared with adults without cancer. Importantly, the proportion of survivors reporting these issues continued a downward trend throughout our observation period in the years following the implementation of the Affordable Care Act. Our findings suggest incremental improvement in health care access and affordability after recent health care reform and provide an important benchmark as additional changes are likely to occur in the coming years.
Identification and Localization of a Beta-1 Receptor from the Integrin Family in Mammalian Retinal Pigment Epithelial Cells

The distribution of an adhesion receptor from the integrin family was mapped in cultured mammalian retinal pigment epithelial cells (RPE), and in primate RPE cells in vivo, using antibodies to the human fibronectin receptor (FnR) in conjunction with indirect immunofluorescence and immunoelectron microscopy. Protein homogenates from human RPE or MG-63 cells were separated by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) under nonreducing conditions. On Western blots of proteins from both cell types, anti-FnR and a monoclonal antibody to the /?i subunit of human FnR each recognized a single band with a molecular mass of approximately 115 kDa. After 1-6 weeks in culture human, monkey and feline RPE cells gradually acquired a morphology and cytoskeletal arrangement typical of a mature cuboidal epithelium. The distribution of anti-FnR labeling changed dramatically in accordance with the cells' phenotype. In preconfluent cells, labeling consisted of streaks and flecks of fluorescence at the termini of stress fibers and at putative sites of cell substratum attachment. As the cells became confluent and acquired an epithelioid morphology, the bulk of anti-FnR labeling shifted to the peripheral cytoplasm and appeared as a cross-hatched meshwork. In fully differentiated RPE cells anti-FnR labeling consisted of a dense punctate pattern on or close to the apical cell surface that coincided with the distribution of f-actin as shown by phalloidin staining, and to the distribution of apical microvilli as identified by scanning electron microscopy. In addition, a compacted rim of fluorescence appeared at the cells' lateral margins that was also virtually identical to the phalloidin staining pattern. No basal surface labeling was apparent at this stage. At the ultrastructural level, FnR was localized to the apical surface of nonpermeabilized RPE cells and, in particular, to the plasma membrane of apical microvilli in vitro and in vivo using an indirect, pre-embedding method. The results strongly suggest that: (1) a membrane receptor/s containing the integrin 0i subunit is normally present on the plasma membrane of apical microvilli and on the lateral cell surfaces of cultured mammalian RPE cells; and (2) this receptor also is present on the plasmalemma of RPE apical microvilli in vivo. Invest Ophthalmol Vis Sci 31:81-93,1990
Mitochondria - Releasing Power for Life and Unleashing the Machineries of Death

The mitochondrion has long been known both as a chemical powerplant and as a cellular compartment housing various biosynthetic pathways. However, studies on the function of mitochondria in apoptotic cell death have revealed a versatility and complexity of these organelles previously unsuspected. The mechanisms proposed for mitochondrial involvement in cell death are diverse and highly controversial. In one model, mitochondria are seen as passive containers that can be made to leak out cytotoxic proteins. In other scenarios, however, certain more or less familiar aspects of mitochondrial physiology, such as oxidative phosphorylation, generation of oxygen radicals, dynamic morphological rearrangements, calcium overload, and permeability transition, are proposed to play crucial roles. In this review, we examine a few promising mechanisms that have been gaining attention recently.
Indigenous Children’s Rights and Well-Being: Perspectives from Central and Southern Africa

In this chapter, the issue of children’s rights in Central and Southern Africa, with particular reference to indigenous peoples, specifically the Batwa of Central Africa and the San of Southern Africa. These populations historically suffered massive human rights violations. Their civil and political rights and social, economic, and cultural rights are not recognized, and they represent some of the most disadvantaged people on the African continent. The chapter looks at some of the difficulties that Batwa and San children face in the area of education. In schools Batwa and San children have had to cope with mistreatment at the hands of teachers, administrators, and other students, often leading to high dropout rates. Some of the areas of concern relate to boarding schools and hostels and to the need for mother-tongue education and a culturally relevant curriculum. Drawing on data from Central and Southern Africa, specifically the Democratic Republic of Congo, Burundi, Gabon, Uganda, and the Republic of Botswana, this chapter assesses some of the challenges facing indigenous students. Additionally, examples of ways that education can be approached in order to facilitate greater opportunities for indigenous children are also presented.
Arabidopsis as a Model to Develop Strategies for the Modification of Seed Oils

Modifying the fatty acid composition of the triacylglyerols in oilseeds is an attractive goal in plant biotechnology since it will allow the production of improved vegetable oils for food and manufacturing industries. Mutants of Arabidopsis with defects in lipid metabolism have greatly increased our understanding of the pathways of lipid biosynthesis in leaves and seeds. Mutations have been identified that, in seed tissue, cause deficiencies in the elongation of 18:1 to 20:1, desaturation of 18:1 to 18:2, and desaturation of 18:2 to 18:3. In each of these cases, the wild type exhibited incomplete dominance over the mutant allele. These results, along with results from earlier studies, point to a major influence of gene dosage in determining the fatty acid composition of seed lipids. The advantages of Arabidopsis as a model for plant molecular genetics will allow the mutants to be used as a means to clone the lipid metabolism genes by chromosome walking or insertion mutagenesis. Because of the time and effort required by these approaches, it is important to identify the genes which hold the greatest promise for usefully altering plant lipid composition. In this paper, we discuss strategies for modifying the fatty acid composition of seed oils based on our present understanding of the biochemistry and genetics of seed lipid synthesis.
Time-Invariant Strategies in Coordination of Human Reaching

This paper addresses validation of a curvature-theory-based time-invariant inverse kinematic model and a related tracking algorithm for human motor control of reaching motions. Human subjects made unconstrained reaching motions in the horizontal plane to fixed targets at three self-selected speeds. Consistent shoulder/elbow joint speed ratios for motions to the same target across speeds were observed, indicating a time-invariant planning strategy. The inverse kinematic model’s technique of relating joint motions with a Taylor series expansion is in concert with the leading joint hypothesis. With this approach the tracking algorithm successfully replicated the experimental wrist trajectories, and also predicted the previously observed elbow-led motions for reaching in the ipsilateral hemifield. The elbow leads the arm motion in this hemifield because the shoulder approaches a dwell. A computationally frugal strategy of intermittent path correction based on two error parameters is proposed.
Daratumumab induces CD38 internalization and impairs myeloma cell adhesion

Daratumumab (Dara), a human immunoglobulin G1 kappa (IgG1κ) monoclonal anti-CD38 antibody, has been approved by the U.S. Food and Drug Administration for the treatment of relapsed multiple myeloma (MM) as a single agent as well as in combination with immunomodulatory drugs (IMiDs) and proteasome inhibitors (PI). Although the scientific rationale behind the use of Dara in combination with IMiDs has been extensively explored, the molecular mechanisms underlying Dara-PI regimens have not yet been investigated. Here, we demonstrate that CD38 on the surface of MM cells is rapidly internalized after Dara treatment; we also show that Dara treatment impairs MM cell adhesion, an effect that can be rescued by using the endocytosis inhibitor Dynasore. Finally, we show that Dara potentiates bortezomib (BTZ) killing of MM cells in vitro and in vivo, independent of its function as an immune activator. In conclusion, our data show that Dara impairs MM cell adhesion, which results in an increased sensitivity of MM to proteasome inhibition.
Case 8: Extracapsular Cataract Extraction Wound Rupture

An 84-year-old man with history of extracapsular cataract extraction (ECCE) in both eyes 30 years prior presented with a Zone II open globe injury of the left eye secondary to ECCE wound dehiscence following blunt trauma. The patient underwent repair of his open globe injury and required several secondary retinal surgeries. The patient achieved a post-operative visual acuity of 20/125; however, he subsequently developed a retinal detachment resulting in a visual acuity of counting fingers. This case illustrates the poor prognosis and multiple complications associated with open globe injury following ECCE surgery.
Insight and Self-Observation

The subtitle, “On Reading Minds,” is not without risk in a symposium of experts on schizophrenia, particularly if it suggests a cookbook set of directions. However, the way one reads minds is clear; it is similar to the way one reads books. One listens to what someone else has to say, and hears what that person has in mind; not everything in his mind, and not necessarily accurately what is in his mind, but something of what he has in mind. This is a wonderful and improbable set of phenomena: that thoughts are quickly transferred back and forth between two organisms in a universe which, at first glance, would not seem to be a likely place for such an occurrence.
Development of a rapid ultra performance hydrophilic interaction liquid chromatography tandem mass spectrometry method for procyanidins with enhanced ionization efficiency.

Abstract Cocoa flavanols (catechins and procyanidins) can exist in various polymerization states and are commonly classified by their degree of polymerization (DP). There is increasing evidence that flavanols of distinct DP possess different biological activities, but separation and quantification of the higher DP procyanidins is challenging and has thus created the need for new methodologies that utilize advancements in columns and LC–MS/MS systems. An aqueous normal phase (hydrophilic interaction liquid chromatography, HILIC), UPLC method with post-column ESI adjuvant infusion was developed to reduce the total analysis time, increase peak separation, and increase detection specificity (compared to traditional fluorescence methods) by coupling with mass spectrometry detection. The total elution time was reduced from 70 to 90 min (typically used for normal phase and HILIC HPLC separation of procyanidins) down to 9 min by employing UPLC. Results indicate that by using a post-column 0.04 M ammonium formate infusion (5 μL/min), ionization of procyanidins was significantly enhanced. Lower limits of detection ranged from 3.19 × 10−2 to 4.56 pmol-on-column, and lower limits of quantification ranged from 2.79 × 10−2 to 1.17 × 102 pmol-on-column across compounds DP 1–9. This method builds upon the foundation set by existing analytical methods and employs new technologies to dramatically increase sample throughput and enhance detection limits and specificity, facilitating improved analysis for procyanidins.
Hutchinson-Gilford Progeria Syndrome: Challenges at Bench and Bedside

The structural nuclear proteins known as "lamins" (A-type and B-type) provide a scaffold for the compartmentalization of genome function that is important to maintain genome stability. Mutations in the LMNA gene -encoding for A-type lamins- are associated with over a dozen of degenerative disorders termed laminopathies, which include muscular dystrophies, lipodystrophies, neuropathies, and premature ageing diseases such as Hutchinson Gilford Progeria Syndrome (HGPS). This devastating disease is caused by the expression of a truncated lamin A protein named "progerin". To date, there is no effective treatment for HGPS patients, who die in their teens from cardiovascular disease. At a cellular level, progerin expression impacts nuclear architecture, chromatin organization, response to mechanical stress, and DNA transactions such as transcription, replication and repair. However, the current view is that key mechanisms behind progerin toxicity still remain to be discovered. Here, we discuss new findings about pathological mechanisms in HGPS, especially the contribution of replication stress to cellular decline, and therapeutic strategies to ameliorate progerin toxicity. In particular, we present evidence for retinoids and calcitriol (hormonal vitamin D metabolite) being among the most potent compounds to ameliorate HGPS cellular phenotypes in vitro, providing the rationale for testing these compounds in preclinical models of the disease in the near term, and in patients in the future.
Comparison of three approaches for synchronization of ovulation for timed artificial insemination in Bos indicus-influenced cattle managed on the Texas gulf coast

Our objectives were to compare the relative efficacies of three protocols designed to synchronize ovulation for timed artificial insemination (AI) of predominantly Brahman-influenced cows and heifers. In Exp. 1, 273 Brahman x Hereford (F1) cows at three locations were stratified by BW, body condition score (BCS), age, and days postpartum and assigned randomly to three treatments: 1) Syncro-Mate-B (SMB), 2) norgestomet-prostaglandin (NP), and 3) Ovsynch. The management goal required that cows have a minimum BCS of 5 and be at least 36 d postpartum (PP) at treatment onset. However, final results included 23 cows (8.4%) whose BCS fell below 5. In Exp. 2, 286 pubertal beef heifers were stratified by BW and BCS and allocated randomly to the three treatments. Heifers were predominantly Brahman crossbred (n = 265; Brahman x Hereford, F1; Santa Cruz) or purebred Brahman-influenced (Santa Gertrudis) with a smaller number (n = 21) of Hereford heifers also included. For both experiments, SMB treatment consisted of a 9-d norgestomet ear implant plus an estradiol valerate/norgestomet injection on d 0. Norgestomet-prostaglandin-treated females were implanted with a SMB implant without the estradiol valerate/norgestomet injection at the time of implant insertion and received 25 mg prostaglandin F2alpha (PGF) i.m. 2 d before implant removal. Ovsynch consisted of 100 microg GnRH i.m. on d 1, 25 mg PGF i.m. on d 8, and a second GnRH injection on d 10. Beginning on d 9, calves were removed for 48 h in Exp. 1. Cattle in SMB and NP groups in both experiments were timed-inseminated 48 to 54 h after implant removal and at 12 to 24 h after the second GnRH injection (Ovsynch). Timed AI conception rates did not differ between the SMB (45.1%) and Ovsynch (42.4%) groups; however, conception rate in the NP group tended (P < 0.12) to be lower overall than in the other groups due to a reduced (P < 0.05) conception rate in cows that were < 60 d PP at treatment onset. Conversely, timed-AI conception was greatest (P < 0.056) in NP (54.7%) compared with SMB (40.4%) and Ovsynch (39.1%) for heifers in Exp. 2. We conclude that in mature, suckled beef cows with Brahman genetic influence, SMB and Ovsynch perform similarly when cow eligibility relies primarily on BCS and minimum days PP. The NP treatment results in lower conception in cows < 60 d PP compared with SMB and Ovsynch. However, in nulliparous Brahman-influenced heifers that are confirmed to be pubertal, NP may be superior to the other two treatments for timed AI.
The transcriptional co-activator NCOA6 promotes estrogen-induced GREB1 transcription by recruiting ERα and enhancing enhancer–promoter interactions

Estrogen and its cognate receptor, ERα, regulate cell proliferation, differentiation, and carcinogenesis in the endometrium by controlling gene transcription. ERα requires co-activators to mediate transcription via mechanisms that are largely uncharacterized. Herein, using growth-regulating estrogen receptor binding 1 (GREB1) as an ERα target gene in Ishikawa cells, we demonstrate that nuclear receptor co-activator 6 (NCOA6) is essential for estradiol (E2)/ERα–activated GREB1 transcription. We found that NCOA6 associates with the GREB1 promoter and enhancer in an E2-independent manner and that NCOA6 knockout reduces chromatin looping, enhancer–promoter interactions, and basal GREB1 expression in the absence of E2. In the presence of E2, ERα bound the GREB1 enhancer and also associated with its promoter, and p300, myeloid/lymphoid or mixed-lineage leukemia protein 4 (MLL4), and RNA polymerase II were recruited to the GREB1 enhancer and promoter. Consequently, the levels of the histone modifications H3K4me1/3, H3K9ac, and H3K27ac were significantly increased; enhancer and promoter regions were transcribed; and GREB1 mRNA was robustly transcribed. NCOA6 knockout reduced ERα recruitment and abolished all of the aforementioned E2-induced events, making GREB1 completely insensitive to E2 induction. We also found that GREB1-deficient Ishikawa cells are much more resistant to chemotherapy and that human endometrial cancers with low GREB1 expression predict poor overall survival. These results indicate that NCOA6 has an essential role in ERα-mediated transcription by increasing enhancer–promoter interactions through chromatin looping and by recruiting RNA polymerase II and the histone-code modifiers p300 and MLL4. Moreover, GREB1 loss may predict chemoresistance of endometrial cancer.
Late-Onset Neonatal Sepsis in a Patient with Covid-19.

Late-Onset Neonatal Sepsis with Covid-19 The condition of a 3-week-old boy with nasal congestion, tachypnea, and reduced feeding deteriorated, and he underwent intubation and received hemodynamic s...
Response Advantage for the Identification of Speech Sounds

The ability to distinguish among different types of sounds in the environment and to identify sound sources is a fundamental skill of the auditory system. This study tested responses to sounds by stimulus category (speech, music, and environmental) in adults with normal hearing to determine under what task conditions there was a processing advantage for speech. We hypothesized that speech sounds would be processed faster and more accurately than non-speech sounds under specific listening conditions and different behavioral goals. Thus, we used three different task conditions allowing us to compare detection and identification of sound categories in an auditory oddball paradigm and in a repetition-switch category paradigm. We found that response time and accuracy were modulated by the specific task demands. The sound category itself had no effect on sound detection outcomes but had a pronounced effect on sound identification. Faster and more accurate responses to speech were found only when identifying sounds. We demonstrate a speech processing "advantage" when identifying the sound category among non-categorical sounds and when detecting and identifying among categorical sounds. Thus, overall, our results are consistent with a theory of speech processing that relies on specialized systems distinct from music and other environmental sounds.
Zu Aktualität und Methode von Kapitalismuskritik: Victor Kempf verfasst eine hervorragende sozialphilosophische Betrachtung

Rezension von: Victor Kempf (2019): Exodus oder dialektische Negation. Paradigmen der Kapitalismuskritik im Widerstreit, Wiesbaden: Springer VS.
Surgeon-level variance in achieving clinical improvement after lumbar decompression: the importance of adequate risk adjustment.

Abstract BACKGROUND CONTEXT Patient-Reported Outcome Measurement Information System (PROMIS) scores are increasingly utilized in clinical care. However, it is unclear if PROMIS can discriminate surgeon performance on an individual level. PURPOSE The purpose of this study was to examine surgeon-level variance in rates of achieving minimal clinically important difference (MCID) after lumbar decompression. PATIENT SAMPLE This is a prospective, observational cohort study performed across a healthcare enterprise (two academic medical centers and three community centers). Patients 18 years or older undergoing one- to two-level primary decompression for lumbar disc herniation (LDH) or lumbar spinal stenosis (LSS) were included. OUTCOME MEASURES The primary outcome was achievement of MCID, using a distribution-based method, on paired PROMIS physical function scores. METHODS Descriptive statistics were generated to examine the baseline characteristics of the study cohort. Bivariate analyses were used to examine the impact of surgeon-level variance on rates of MCID. Multivariable analyses were used to examine the risk-adjusted impact of surgeon-level variance on rates of MCID. RESULTS Overall, 636 patients treated by nine surgeons were included. The median patient age was 58 [interquartile range (IQR): 46–70] and 62.3% (n=396) were female. Among all patients, 56.9% (n=362) underwent surgery for LDH. The overall rate of achieving MCID was 75.8% (n=482). Of the surgeons, the median years in practice were 12 (range 4–31) and 55.6% (n=5) were in academic practice settings. On bivariate analysis, patients treated by one of the surgeons had lower rates of achieving MICD (odds ratio=0.37, 95% confidence interval: 0.15–0.91, p=.03). However, on multivariable analysis adjusting for operative indication (LDH vs. LSS), body mass index, number of comorbidities, percent unemployment in patient zip code, and preoperative PROMIS physical function scores, all surgeons were equally likely to obtain MCID. CONCLUSIONS In this cohort, variance in PROMIS scores after primary lumbar decompression is influenced by patient-related factors and not by individual surgeon. Adequate risk adjustment is needed if ascertaining clinical improvement on an individual surgeon basis. Level of Evidence 2
Breastfeeding Experiences of Baccalaureate Nursing Students: A Qualitative Study:

BackgroundStudents returning to school who are breastfeeding face unique challenges. There is limited literature on breastfeeding university students. Several researchers have studied breastfeeding...
A Fully Coherent Array for Evaporation Duct Height Estimation at Coastal Boundaries

The Coherent Vertical Array (CoVA) system has been designed to be used during the Coastal Land-Air-Sea Interactions (CLASI) mission for evaporation duct height (EDH) estimation by measuring the grazing angle of the incident, ducted signal. High angular resolution and phase coherence is needed in the CoVA system due to the ducted signal having a narrow grazing angle with small variations translating to large variations in EDH estimation. This paper discusses the design of the CoVA system and the methodology used to achieve high phase coherence. The results obtained by CoVA during CLASI will be presented in future work.
Health Behavior Combinations and Their Association With Inflammation

Abstract Purpose. Studies have examined the independent and additive effects of health behaviors (e.g., physical activity, diet, sleep, and smoking) on systemic inflammation, but we know little about whether different pairs of these behaviors differentially influence inflammation, which was the purpose of this study. Design. Cross-sectional. Setting. The National Health and Nutrition Examination Survey (NHANES) 2005–2006. Subjects. A total of 2051 adults (≥20 years). Measures. A questionnaire/interview was used to assess sleep and dietary behavior; physical activity was assessed via accelerometry; smoking was assessed via cotinine levels; and a blood sample was taken to assess systemic inflammation (C-reactive protein; [CRP]). Analysis. Multivariable linear regression analysis. Results. Six health behavior pairs were evaluated: (1) active and healthy diet, (2) active and adequate sleep, (3) active and nonsmoker, (4) healthy diet and adequate sleep, (5) healthy diet and nonsmoker, and (6) adequate sleep an...
Divided We Fall: State College and the Normal School Movement in Kentucky, 1880-1910

As the 1905 school year opened, James K. Patterson faced his most serious challenge since overseeing the establishment of the Agricultural and Mechanical College of Kentucky as an inde pendent institution more than a quarter of a century earlier. For nearly three decades the elderly, aloof, and somewhat cantan kerous educator had been recognized as the leading spokesperson for public higher education in the Commonwealth. A teacher in Kentucky since before the Civil War, Patterson had been on the original faculty of the A&M College when it was founded in 1866 as part of Kentucky University. President Patterson had devel oped a reputation for toughness, if not stubbornness, and State College virtually consumed his life. Even though the college historically had been underfunded, and perhaps underappreciated, Patterson believed that State College was the true hope for Ken tucky's educational future. But now Patterson found himself embroiled in a debate over teacher education that ironically threatened to fragment the state's education dollars as new insti tutions were created to train the teachers so desperately needed for Kentucky's growing number of common schools.1 In 1878, the Agricultural and Mechanical College separated from Kentucky University and was chartered by the General Assembly as the state's only public institution for higher educa tion. Under the leadership of Patterson, the A&M College was offered land for its campus on Lexington's south side in a fifty eight-acre park. Two years later, the General Assembly passed
Optimal Ge/SiGe nanofin geometries for hole mobility enhancement: Technology limit from atomic simulations

We use first principles simulations to engineer Ge nanofins for maximum hole mobility by controlling strain tri-axially through nano-patterning. Large-scale molecular dynamics predict fully relaxed, atomic structures for experimentally achievable nanofins, and orthogonal tight binding is used to obtain the corresponding electronic structure. Hole transport properties are then obtained via a linearized Boltzmann formalism. This approach explicitly accounts for free surfaces and associated strain relaxation as well as strain gradients which are critical for quantitative predictions in nanoscale structures. We show that the transverse strain relaxation resulting from the reduction in the aspect ratio of the fins leads to a significant enhancement in phonon limited hole mobility (7× over unstrained, bulk Ge, and 3.5× over biaxially strained Ge). Maximum enhancement is achieved by reducing the width to be approximately 1.5 times the height and further reduction in width does not result in additional gains. These results indicate significant room for improvement over current-generation Ge nanofins, provide geometrical guidelines to design optimized geometries and insight into the physics behind the significant mobility enhancement.
Posttranslational regulation of sucrase-isomaltase expression in intestinal crypt and villus cells.

Abstract Expression and synthesis of sucrase-isomaltase (SI) were studied in human jejunum and in the colon tumor cell lines Caco-2 and HT-29. Twelve monoclonal antibodies produced against the adult human intestinal enzyme were shown to recognize specifically SI by immunoprecipitation of 14C-labeled membrane proteins, analysis of enzyme activities in the immunoprecipitates, and immunoblotting. These antibodies produced markedly different patterns of immunofluorescent staining of the intestinal mucosa. Three of them were specific for the absorptive villus cells, while the other nine also stained the luminal membrane of the proliferative crypt cells, with different intensities which paralleled their ability to recognize SI in immunoblots. Sequential immunoprecipitation of SI solubilized from purified brush borders or entire jejunum with four selected antibodies demonstrated the presence of different forms of the enzyme, expressed by either villus or crypt cells. Two immunologically distinct forms of high mannose precursor (hmP1 and hmP2) were also identified in both jejunal mucosa and colon tumor cells. They were present as monomers and their immunological differences were preserved under various ionic and pH conditions. Pulse-chase studies indicated that, in Caco-2 cells, hmP1 is converted into hmP2 within 30 min of chase, and hmP2 is then processed into the complex-glycosylated precursor destined for the brush border membrane. hmP1 was immunologically related to the mature SI present in crypt cells and lacked the epitopes specific for mature SI expressed by villus cells. These results demonstrated that sucrase-isomaltase is synthesized by both crypt and villus cells, but processing of the cotranslationally glycosylated high mannose precursor is dependent on the state of differentiation of the enterocytes. This may represent a general mechanism for the regulation of expression of differentiated cell products at the post-translational level.
When Did the Switch in Time Actually Occur?: Re-Discovering the Supreme Court's Forgotten Decisions of 1936-37

This article offers insights into the Court-packing controversy of 1937 by analyzing the U.S. Supreme Court's decisions between the election of 1936 and President Roosevelt's announcement of his Court-packing proposal in February 1937. These forgotten decisions, which scholars have either ignored or neglected to consider in their political context, sustained the constitutionality of a wide range of economic regulatory legislation and helped to expand personal liberties. Although this article contends that these decisions were too little and too late to discourage Roosevelt from proceeding with his Court-packing plan, the article argues that these decisions went far toward restoring public confidence in the Court and helped to turn public opinion against the Court-packing bill even before the Court's so-called switch in time during the spring of 1937. The article, which devotes special attention to the voting patterns of Chief Justice Hughes and Justice Roberts in these decisions, also argues that the election had little direct impact on these decisions, but that general changes in attitudes toward economic regulation may have influenced the Court.
Multiple Imputation of Dental Caries Data Using a Zero Inflated Poisson Regression Model

Excess zeros exhibited by dental caries data require special attention when multiple imputation is applied to such data. Objective To demonstrate a simple technique using a zero-inflated Poisson (ZIP) regression model, to perform multiple imputation for missing caries data.