cssi/SciSciGPT-SciSciNet huggingface dataset:
Frontline hyper-CVAD plus ponatinib for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Updated results of a phase II study.

7013Background: The combination of chemotherapy plus a TKI is highly effective in Ph+ ALL. In this phase II study, we evaluated the safety and efficacy of HCVAD in combination with the third-generation pan-BCR-ABL inhibitor, ponatinib. Methods: Patients (pts) with newly diagnosed Ph+ ALL received 8 cycles of HCVAD alternating with high dose MTX/Ara-C every 21 days. Ponatinib was given at 45 mg daily for the first 14 days of cycle 1. Initially ponatinib 45 mg daily was given indefinitely beginning at cycle 2. Due to concern for vascular events, a protocol amendment was made in which, beginning in cycle 2, pts in CR received 30mg daily and pts in CMR received 15mg daily. Rituximab and IT chemotherapy were given with the first 4 courses. After 8 cycles of HCVAD, pts in CR received maintenance with ponatinib, vincristine and prednisone for 2 years followed by indefinite ponatinib. Results: 64 pts have been treated, 10 of whom had received prior treatment with another regimen (8 in CR, 2 not in CR). Median age...
Terahertz spectroscopy of vibrational anharmonicity in crystalline γ-aminobutyric acid

Vibrational anharmonicity in molecular solids is of key importance for fundamental physical properties such as thermal expansion and specific heat capacity. In solids, anharmonic character is largely dictated by intermolecular forces, and can be assessed using terahertz vibrational spectroscopy to probe the sub-100cm−1 motions. Significant anharmonicity can be readily identified by anomalous red shifting of terahertz spectral peaks with sample cooling, as seen in the neurotransmitter γ-aminobutyric acid (GABA). The potential energy surface of the lowest-frequency lattice vibration in crystalline GABA was investigated in this work using solid-state density functional theory, which revealed a large deviation from harmonic character. A method for accounting for such anharmonic motion in crystals is presented based on numerical sampling of the potential energy surfaces and the quasi-harmonic approximation (QHA).
Ruthenium(0)-Catalyzed Cycloaddition of 1,2-Diols, Ketols, or Diones via Alcohol-Mediated Hydrogen Transfer

Merging the characteristics of transfer hydrogenation and carbonyl addition, a broad new class of ruthenium(0)-catalyzed cycloadditions has been developed. As discussed in this Minireview, fused or bridged bicyclic ring systems are accessible in a redox-independent manner in C-C bond-forming hydrogen transfer reactions of diols, α-ketols, or 1,2-diones with diverse unsaturated reactants.
Kinetics of nitrous oxide production from hydroxylamine oxidation by birnessite in seawater

Abstract This study characterized the kinetics of abiotic production of the greenhouse gas nitrous oxide (N 2 O) by chemical oxidation of the nitrification intermediate hydroxylamine (NH 2 OH) in seawater at circumneutral pH (6.2–8.3). The oxidant was birnessite , a ubiquitous manganese oxide mineral in a variety of marine environments. Experiments using microsensor electrodes for high-resolution measurements of N 2O production combined with the simultaneous measurements of the removal of NH2OH using spectrophotometric techniques revealed that the reaction was overall first order with the rate law d[N2O]/dt = k[NH2OH]0.9[MnO2]0.3[H+]0 where k is 0.01 s−1. Birnessite consistently oxidized 80–100% of NH2OH to N2O within 3 min. Mass balance on nitrogen indicated rapid formation and disappearance of an intermediate species that was evidently involved in the formation of N2 O. In the presence of a nitroxyl (HNO) scavenger, N 2O production rates and yield were suppressed by 17–59% and ~50%, respectively, suggesting that HNO is an intermediate in NH2OH oxidation to N2 O. These results support a mechanism whereby Mn(IV) is reduced to Mn(III) with the formation of an aminoxyl radical as the first product of NH 2OH oxidation, which donates a second electron to another Mn(IV) center, or reduces the same Mn(III), to release Mn2+ and HNO in solution. The final step is predicted to be HNO dimerization to N 2O given the complete oxidation of NH2OH to N2O at steady-state. The experimentally-derived second-order rate constant for the dimerization step suggests that adsorption of HNO onto the excess solid surface controls the rate of N2O formation. Our findings suggest that abiotic NH2OH oxidation could be an important source of N2 O in coastal ecosystems such as open oceans and oxygen minimum zones as well as sediment ecosystems wherever nitrification occurs in the presence of particulate metal oxides .
Culturally Appropriate Assessment

The chapter provides comprehensive assessment techniques in relation to race, gender, sexual orientation, class, disability/impairment, age, religion, language, region, and multiple identities and their intersections. It illustrates how by providing specific examples. The chapter discusses the foundation for accurate assessment which is formulated by integrating linear and nonlinear, affective and cognitive, and scientific and clinical inquiry. The importance of the intake being taken by the provider who is going to provide therapy is emphasized since the intake provides rich text for treatment strategy. It reveals the client’s worldview, problem-solving strategies, values and beliefs, etc.
Niche partitioning as a mechanism for locally high species diversity within a geographically limited genus of blastoid.

Deltoblastus batheri and Deltoblastus delta occur concurrently in many Permian deposits from Timor. Closely related sister species living in direct proximity without alteration in feeding habit would be in direct violation of Lotka-Volterra dynamics. These two species were measured and compared to see if any evidence of differentiation along feeding lines has occurred in order to reduce direct competition. P-values obtained via Student’s t test display significant differentiation across all measured parameters. Thin-plate splines were used to visualize these differences, and clearly show the differences which are focused on the ambulacral region of the blastoids, which are the primary food gathering point for these species.
Evaluation of Visualization Heuristics

Multiple sets of heuristic have been developed and studied in the Human Computer Interaction (HCI) domain as a method for fast, lightweight evaluations for usability problems. However, none of the heuristics have been adopted by the information visualization or the visual analytics communities. Our literature review looked at heuristic sets developed by Nielsen and Molich [7] and Forsell and Johansson [1] to understand how these heuristics were developed and their intended applications. We also reviewed heuristic studies conducted by Hearst and colleagues [2] and Vaataja and colleagues [10] to determine how individuals apply heuristics to evaluating visualization systems. While each study noted potential issues with the heuristic descriptions and the evaluator’s familiarity with the heuristics, no direct connections were made. Our research looks to understand how individuals with domain expertise in information visualization and visual analytics could use heuristics to discover usability problems and evaluate visualizations. By empirically evaluating visualization heuristics, we can identify the key ways that these heuristics can be used to inform the visual analytics design process. Further, they may help to identify usability problems that are and are not task specific. We hope to use this process to also identify missing heuristics that may apply to designs for different analytic purposes.
Sustaining change towards racial equity through cycles of inquiry

Many national, state, and institutional policies and initiatives advocate for change in higher education through structured forms of data use. The case study of “Old Main University” presented in this article shows how local reformers ( n =9) drew on data and data use tools provided by a long-term action research project implemented at the university to advance racial equity goals at their university. The case narrative utilizes practice theory, cultural historical activity theory (CHAT), and narrative inquiry to illustrate how administrative leaders and faculty at Old Main University coordinated their efforts in a sustained manner through two cycles of practitioner inquiry that was responsive to policy goals. The findings show that data use is productive to promote racial equity when data and data use protocols are used iteratively and in interaction among practitioners who use them to identify inequities rooted in their own practices. The findings support the conclusion that, to sustain change efforts as long-term (mesogenetic) projects, policy makers and local reformers should plan to iteratively redesign data tools, practices, and policies to institute changes in everyday (microgenetic) work practices. Such purposeful redesign holds potential to re-structure professional interactions, sustain motivation and organizational learning, and acculturate practitioners to equity as a standard of practice.
Assessing Colorectal Cancer Mismatch Repair Status in the Modern Era: A Survey of Current Practices and Re-Evaluation of the Role of Microsatellite Instability Testing

Results of DNA mismatch repair testing are used to detect Lynch syndrome and have prognostic and therapeutic implications among patients with sporadic colorectal carcinomas. Immunohistochemistry for mismatch repair proteins (MLH1, PMS2, MSH2, MSH6) and PCR for microsatellite instability are two established methods for assessing mismatch repair function. Older literature suggested a discordance rate of approximately 5% between these assays, leading some institutions to perform dual testing on all cases. Although universal mismatch repair testing is now recommended by multiple professional organizations, none provide guidelines regarding preferred assays. We surveyed 96 academic and nonacademic institutions to assess Lynch syndrome screening practices and evaluated discordance rates between immunohistochemistry and PCR among 809 colorectal cancers tested in our own institution. Our survey demonstrated no significant differences between academic and nonacademic practices with respect to testing strategies. Eighty six percent performed universal screening, and usually (76%) employed immunohistochemistry on initial biopsy samples. Only 20% employed PCR; these were mostly academic practices that used both immunohistochemistry and PCR (p < 0.01 compared with the nonacademic groups). Loss of MLH1/PMS2 staining was often (90%) followed by either BRAF mutational analysis or MLH1 methylation assays. Only 24% adhered to WHO recommendations to assign histologic grade based on mismatch repair status. We found only 3 cases (0.4%) with discordant immunohistochemistry and PCR results in our own practice: 1 reflected decreased MSH-6 staining in a neoadjuvantly treated microsatellite stable tumor, 1 MLH1-deficient tumor showed diminished MLH1/PMS2 in the tumor compared with internal control, and 1 case reflected an error in the molecular laboratory. Overall, our results showed extremely low discordance between methods assessing mismatch repair status and would suggest immunohistochemistry as the preferred single screening test. PCR can be reserved for cases that show equivocal immunostaining patterns.
The Lcamr Missile

This paper presents a fictional case study of an aerospace firm’s analysis of whether to undertake a new missile program for sale in foreign markets. The adoption of this new program will affect fully allocated accounting costs on all of its programs. The issue explored is whether and how the firm ought to take into account the fact that the prices it receives on many of the products it sells to the U.S. government are based on fully allocated accounting costs and how this potentially affects the firm’s incentives to produce as efficiently as possible
Adult and newborn rat inner retinal oxygenation during carbogen and 100% oxygen breathing. Comparison using magnetic resonance imaging delta Po2 mapping.

PURPOSE To test the hypothesis that breathing carbogen (95% O2-5% CO2) oxygenates the inner retina better than breathing 100% oxygen using an magnetic resonance imaging (MRI) method that noninvasively measures inner retinal oxygenation in normal adult and newborn rats. METHODS Urethane-anesthetized adult and newborn (day 18) rats were studied. Sequential images were acquired in room air combined with either 100% oxygen or carbogen breathing. Normalized vitreous signal intensity changes were converted to oxygen tension changes (delta PO2) either on a pixel-by-pixel basis or in specific regions of interest. RESULTS Systemic levels of hyperoxia during carbogen or 100% oxygen breathing were not significantly different (P > 0.05). In the adult rat, a significant difference (P = 0.017) was found in the preretinal vitreous delta PO2 during the breathing of either carbogen (130 +/- 9 mm Hg, mean +/- SEM; n = 5) or 100% oxygen (88 +/- 16 mm Hg; n = 5). Agreement was found between the MRI-determined delta PO2 values and literature oxygen microelectrodes data. In the newborn rat, significant differences (P < 0.05) in the preretinal vitreous delta PO2 were found during carbogen (164 +/- 23 mm Hg; n = 3) and oxygen breathing (91 +/- 8 mm Hg; n = 3). CONCLUSIONS MRI delta PO2 mapping demonstrated for the first time that in the normal adult and newborn rat eye, carbogen breathing oxygenates the inner retina better than 100% oxygen breathing.
RNA interference suppression of AGAMOUS and SEEDSTICK alters floral organ identity and impairs floral organ determinacy, ovule differentiation, and seed-hair development in Populus.

The role of the floral homeotic gene AGAMOUS (AG) and its close homologues in development of anemophilous, unisexual catkins has not previously been studied. We transformed two RNA interference (RNAi) constructs, PTG and its matrix-attachment-region flanked version MPG, into the early-flowering female poplar clone 6K10 (Populus alba) to suppress the expression of its two duplicate AG orthologues. By early 2018, six out of 22 flowering PTG events and 11 out of 12 flowering MPG events showed modified floral phenotypes in a field trial in Oregon, USA. Flowers in catkins from modified events had 'carpel-inside-carpel' phenotypes. Complete disruption of seed production was observed in seven events, and sterile anther-like organs in 10 events. Events with strong co-suppression of both the two AG and two SEEDSTICK (STK) paralogues lacked both seeds and associated seed hairs. Alterations in all of the modified floral phenotypes were stable over 4 yr of study. Trees from floral-modified events did not differ significantly (P < 0.05) from nonmodified transgenic or nontransgenic controls in biomass growth or leaf morphology. AG and STK genes show strong conservation of gene function during poplar catkin development and are promising targets for genetic containment of exotic or genetically engineered trees.
Chip Board Interaction Analysis of 22-NM Fully Depeleted Silicon on Insulator (FD-SOI) Technology in Wafer Level Packaging (WLP)

Recently, Wafer Level Packaging (WLP) has been in high demand, especially in mobile device applications as a path to enable miniaturization while maintaining good electrical performance. The relatively inexpensive package cost and simplified supply chain are encouraging other industries to adapt WLP capabilities for radio frequency (RF), communications/sensing (mmWave) and automotive applications. However, to date its application space has been limited to a small die form factor due to challenging chip board interaction (CBI) control. The combination of ultralow dielectric constant (ULK) based advanced silicon technology and WLP is another challenge for industry to overcome.In this article, to systematically address the CBI, a large test vehicle based on 22-nm fully depleted silicon on insulator (FD-SOI) technology platform and WLP technology is described. In particular, CBI during drop test and temperature cycle on board is investigated and its failure mode analysis is discussed. The impact of silicon die thickness and ball grid array (BGA) metallurgy is also explored.
Crystal structure of the human NK1 tachykinin receptor.

The NK1 tachykinin G-protein–coupled receptor (GPCR) binds substance P, the first neuropeptide to be discovered in mammals. Through activation of NK1R, substance P modulates a wide variety of physiological and disease processes including nociception, inflammation, and depression. Human NK1R (hNK1R) modulators have shown promise in clinical trials for migraine, depression, and emesis. However, the only currently approved drugs targeting hNK1R are inhibitors for chemotherapy-induced nausea and vomiting (CINV). To better understand the molecular basis of ligand recognition and selectivity, we solved the crystal structure of hNK1R bound to the inhibitor L760735, a close analog of the drug aprepitant. Our crystal structure reveals the basis for antagonist interaction in the deep and narrow orthosteric pocket of the receptor. We used our structure as a template for computational docking and molecular-dynamics simulations to dissect the energetic importance of binding pocket interactions and model the binding of aprepitant. The structure of hNK1R is a valuable tool in the further development of tachykinin receptor modulators for multiple clinical applications.
Should campaign finance reform aim to level the playing field

Many argue that an important goal of campaign finance reform should be to ensure that competing candidates have roughly equal financial resources with which to contest campaigns. Although there are...
INFECTIVE ENDOCARDITIS TRENDS AMONGST INTRAVENOUS DRUG USERS: AN EXAMINATION OF PRACTICE PATTERNS IN A MID-WESTERN TERTIARY CARE CENTER

Infective endocarditis and the current opioid epidemic continue to rise in prevalence. Physicians need to examine current practices in order to effectively manage these patients. We performed a retrospective institutional review of admissions for infective endocarditis (IE) during 2012 and 2017.
Climate crisis, health equity, and democratic governance: the need to act together

On Friday, 20 September 2019, over 4 million people worldwide participated in the youth-led Global Climate Strike. Emphasizing the dire impacts of the climate crisis on people's health, planetary health, and health equity, participants called for politicians and those with power to listen to the scientists and to the evidence. But who are these politicians and what is the evidence regarding to whom they listen? In the United States (US), critical research documents how the public's will is being subverted-and people and planetary health are being harmed-via changes to the 'rules of the game' that affect democratic governance. Health professionals, organizations, and institutions should encourage civic engagement-for themselves, their staff, members, and study participants-regarding: voter registration; being counted in the 2020 Census; countering partisan gerrymandering; and helping to build strong coalitions addressing profound links between climate change, health equity, and democratic governance.
The Global Sink of Available Potential Energy by Mesoscale Air-Sea Interaction.

The thermal component of oceanic eddy available potential energy (EPE) generation due to air-sea interaction is proportional to the product of anomalous sea surface temperature (SST) and net air-sea heat flux (SHF). In this study we assess EPE generation and its timescale and space-scale dependence from observations and a high-resolution coupled climate model. A dichotomy exists in the literature with respect to the sign of this term, that is, whether it is a source or a sink of EPE. We resolve this dichotomy by partitioning the SST and net heat flux into climatological mean, climatological seasonal cycle, and remaining transient contributions, thereby separating the mesoscale eddy variability from the forced seasonal cycle. In this decomposition the mesoscale air-sea SST-SHF feedbacks act as a 0.1 TW global sink of EPE. In regions of the ocean with a large seasonal cycle, for example, midlatitudes of the Northern Hemisphere, the EPE generation by the forced seasonal cycle exceeds the mesoscale variability sink, such that the global generation by seasonal plus eddy variability acts as a 0.8 TW source. EPE destruction is largest in the midlatitude western boundary currents due to mesoscale air-sea interaction and in the tropical Pacific where SST variability is due mainly to the El Nino-Southern Oscillation. The EPE sink in western boundary currents is spatially aligned with SST gradients and offset to the poleward side of currents, while the mean and seasonal generation are aligned with the warm core of the current. By successively smoothing the data in space and time we find that half of the EPE sink is confined to timescales less than annual and length scales less than 2°, within the oceanic mesoscale band.
Spatial Component Analysis to Mitigate Multiple Testing in Voxel-Based Analysis

Voxel-based analysis provides a simple, easy to interpret approach to discover regions correlated with a variable of interest such as for example a pathology indicator. Voxel-based analysis methods perform a statistical test at each voxel and are prone to false positives due to multiple testing, or when corrected for multiple testing may miss regions of interest. Component based approaches, such as principal or independent component analysis provide an approach to mitigate multiple testing, by testing for correlations to projections of the data to the components. We propose a spatially regularized component analysis approach to find components for image data sets that are spatially localized and smooth. We show that the proposed approach leads to components that are easier to interpret and can improve predictive performance when used with linear regression models. We develop an efficient optimization approach using the Grassmannian projection kernel and a randomized SVD. The proposed optimization is capable to deal with data sets too large to fit into memory. We demonstrate the approach with an application to study Alzheimer’s disease using over 1200 images from the OASIS-3 data set.
Return to Golf Following Reverse Total Shoulder Arthroplasty

Background: The object of this study was to examine return to golf and changes in golf performance after shoulderarthroplasty. Additionally, we set out to determine if there were differences in return to play and performance betweentotal shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (RTSA). We also examined pain during the golfswing to determine if there is a change in pain level after surgery.Methods: Patients were identified using a Current Procedural Terminology code 23472 search for TSA. A 19-questiononline survey was sent out to each patient with questions detailing golfing performance and pain during the swing beforeand after surgery. Comparisons were made to determine differences in pain, performance and enjoyment between TSAand RTSA groups before and after surgery.Results: A total of 586 patients who underwent shoulder arthroplasty were sent the online survey via email. Of thosepatients, 33 identified themselves as golfers and who responded to the survey, resulting in an overall response rate of5.6%. Twenty-three of 31 (74%) patients were able to return to golf following their procedure. Overall, the respondentswho reported pain associated with golfing activity had significantly decreased pain after undergoing either TSA orRTSA. The RTSA group had a significant drop in driving distance following the procedure and this was significantlylower than the postoperative driving distance in the TSA group, despite an insignificant preoperative difference.Conclusion: Overall, TSA offers a safe and effective means for reducing pain during the golf swing in patientssuffering from advanced shoulder osteoarthritis. While there were no significant changes in performance followingTSA, individuals undergoing RTSA can be counseled that they are at risk for lower driving distances due to alteredmechanics. Overall, patients were satisfied with their procedure and their ability to return to the golf course.Level of evidence: IV
ETF Corporate Bond Ownership and Market Quality

This paper examines the role exchange-traded funds (ETFs) play in providing information to underlying corporate bond markets. We document liquidity improvements for individual corporate bonds regardless of market direction. That increased liquidity, however, comes at the cost of greater market sensitivity. Three separate tests show that increased ETF ownership increases the systematic risk component of bond prices and disrupts the flow of firm-specific information to underlying bonds. The results suggest, therefore, that while ETF ownership improves bond market liquidity, ownership is associated with a dissociation between bond prices and firm fundamentals. Mutual fund ownership does not have the same effect, suggesting the active intraday trading that is the hallmark of ETFs may also serve as the mechanism through which information flow is affected.
Experience, but not age, is associated with volumetric mushroom body expansion in solitary alkali bees

In social insects, changes in behavior are often accompanied by structural changes in the brain. This neuroplasticity may come with experience (experience-dependent) or age (experience-expectant). Yet, the evolutionary relationship between neuroplasticity and sociality is unclear, because we know little about neuroplasticity in the solitary relatives of social species. We used confocal microscopy to measure brain changes in response to age and experience in a solitary halictid bee (Nomia melanderi). First, we compared the volume of individual brain regions among newly-emerged females, laboratory females deprived of reproductive and foraging experience, and free-flying, nesting females. Experience, but not age, led to significant expansion of the mushroom bodies-higher-order processing centers associated with learning and memory. Next, we investigated how social experience influences neuroplasticity by comparing the brains of females kept in the laboratory either alone or paired with another female. Paired females had significantly larger olfactory regions of the mushroom bodies. Together, these experimental results indicate that experience-dependent neuroplasticity is common to both solitary and social taxa, whereas experience-expectant neuroplasticity may be an adaptation to life in a social colony. Further, neuroplasticity in response to social chemical signals may have facilitated the evolution of sociality.
Privacy-preserving With Sonification For Training of Convolutional Deep Neural Networks for Melanoma Diagnosis

Melanoma is a form of cancer that is a primary cause of skin cancer deaths. A major predictive factor for positive patient outcomes is diagnosis of disease in earlier cancer stages before the disease has spread beyond the initial lesion. However, many patients are diagnosed late because they cannot afford to meet a doctor or are embarrassed to be examined. These patients suffer from a significantly greater rate of mortality. As a remedy, machine learning models have been proposed to enable easy and automated diagnosis using images. However, the development of models for use in a clinical setting is not yet possible due to the limited availability of training data. Training data that is available is often private and thus isolated within individual institutions. Therefore, a large data set containing patients of different ancestries, skin colors, and ages is not available. In this study, we show that the Sonification of images results in a greater proportion of patients' consent to share their data in a public database, and that models trained from Sonified images have similar performance to those trained on raw skin lesion images.
Violence on Many Sides: Framing Effects on Protest and Support for Repression

The success of protests depends on whether they favorably affect public opinion: nonviolent resistance can win public support for a movement, but regimes counter by framing protest as violent and instigated by outsiders. The authors argue that public perceptions of whether a protest is violent shift based on the framing of the types of action and the identities of participants in those actions. The article distinguishes between three dimensions: (1) threat of harm, (2) bearing of arms and (3) identity of protesters. Using survey experiments in Israel and the United States, the study finds support for framing effects. Threat of harm has the largest positive effect on perceptions of violence and support for repression. Surprisingly, social out-groups are not perceived as more violent, but respondents favor repressing them anyway. Support for repressing a nonthreatening out-group is at least as large as support for repressing a threatening in-group. The findings link contentious action and public opinion, and demonstrate the susceptibility of this link to framing.
Abstract 70: Obesity-induced impairment of antitumor immunity is associated with an immunosuppressive tumor immune landscape

Obesity is associated with an increased risk and progression in a variety of cancers. In melanoma, obesity is associated with an increased risk of recurrence following surgical resection which may reflect immune escape of cancer surveillance. We sought to examine the impact of obesity on antitumor immunity in an immunogenic preclinical melanoma model.Male C57/Bl6 mice were fed a 45% fat diet or 10% fat diet for 12 months resulting in obese (body weight 52.8g ±1.3) vs control mice (body weight 38.8g ±2.2). For these studies, we utilized the YUMMER cell line, a C57BL/6J syngeneic melanoma cell line with three driver mutation/deletions (BrafV600E, Pten-/-, Cdkn2a-/-), irradiated to mimic the high mutation burden of human melanoma. 0.5x106 YUMMER cells were subcutaneously injected into the flank of aged (13 month old) control and obese mice. After 14 days post injection, tumors in control mice either had growth arrest or regression. In contrast, all obese mice exhibited progressively growing tumors with 6-fold greater tumor weights after 21 days as compared to control (1.3g ±0.4 vs 0.23g ±0.06). CyTOF analysis of tumor-infiltrating immune cells at day 21 showed 2-fold decrease in the percentage of CD4 T cells in tumors from obese mice (9.8% vs 21.1% of CD45). In addition, obesity resulted in 4-fold increase in the frequency of intratumoral Treg (26.1% vs 8.3% of CD3CD4 cells) and CD8/Treg ratio was 2-fold reduced in obese mice. In contrast to prior findings in obese mice bearing B16 melanomas, the percentage of CD8 T cells expressing PD1 was similar (80.4% vs 74.3%), but we found 2-fold higher frequency of CD8PD1 T cells co-expressing TIM3 and LAG3 in tumors from obese mice (43.3% vs 23.0%). Moreover, obesity also attenuated the frequency of tumor-infiltrating cDC2 (1.4% vs 3.5% of CD45) but did not affect NK cells or B cell proportions. Furthermore, the ratio of tumor infiltrating myeloid cells to T cells was higher in obese mice (1.94:1 vs 0.82:1). Moreover, myeloid cells from obese mouse tumors had higher expression of PDL1, CD206, and CD38 markers.Our findings provide evidence that obesity impairs antitumor immunity by modulating the relative abundance of intratumoral immune cell populations and their phenotypes to promote immunosuppressive microenvironment. These findings will be validated in subsequent studies and examined in human specimens. Citation Format: Barbara Pazdrak, Duncan Mak, William Damsky, Marcus Bosenberg, Brooklyn Lochmann, Matthew Gubin, Jennifer McQuade. Obesity-induced impairment of antitumor immunity is associated with an immunosuppressive tumor immune landscape [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 70.
Republic of Women: Rethinking the Republic of Letters in the Seventeenth Century

Republic of Women recaptures a lost chapter in the narrative of intellectual history. It tells the story of a transnational network of female scholars who were active members of the seventeenth-century republic of letters and demonstrates that this intellectual commonwealth was a much more eclectic and diverse assemblage than has been assumed. These seven scholars - Anna Maria van Schurman, Princess Elisabeth of Bohemia, Marie de Gournay, Marie du Moulin, Dorothy Moore, Bathsua Makin and Katherine Jones, Lady Ranelagh - were philosophers, schoolteachers, reformers and mathematicians. They hailed from England, Ireland, Germany, France and the Netherlands, and together with their male colleagues - men like Descartes, Huygens, Hartlib and Montaigne - they represented the spectrum of contemporary approaches to science, faith, politics and the advancement of learning. Carol Pal uses their collective biography to reconfigure the intellectual biography of early modern Europe, offering a new, expanded analysis of the seventeenth-century community of ideas.
Animate Vision, Virtual Environments, and Neural Codes

Publisher Summary A crucial problem to solve in a real-time model of behavior is that of interrupts: How does one know when to change the current agenda? One idea is that of completely predicting aspects of the environment. If an agent could predict its perceptions in a literal way, then deviations from these predictions could be used to change focus. The huge complicating issue is that perceptions are hugely vary from instance to instance owing in part to view variations, and therefore, perhaps arguably impossible to predict. However, this problem could be tackled with time-varying histograms and linear prediction methods. In order to understand the role of the constraints of the human body in cognition, one must have a working human body. Standard humanoid graphics model have a very restricted repertoire of movements. One needs accurate physical models of reaching and grasping in order to simulate how long they take and the errors they make. Understanding such movements is a big problem, however a lightweight approach is chosen that generates movements using equilibrium points (EP) and Jacobian approximations. With these a small number of parameter movements are generated that are both realistic enough to be useful and compact enough to be accessible to expected reward methods.
Surface micromachined sensors for vehicle and personal navigation systems

Vehicle navigation systems rely for the most part on GPS receivers to derive position and provide route guidance and vehicle tracking. GPS signal reception is not always 100% reliable however, necessitating backup from a supplemental system capable of performing dead reckoning. For short periods of time, this function can be filled by a combination of a gyroscope and accelerometer(s). Over the past few years, significant progress has been made in the field of surface micromachining, allowing semiconductor manufacturers to bring to market accelerometers using this new technology. Analog Devices' ADXL202 is one example of such accelerometers capable of achieving sufficient accuracy at the low cost required for a viable and practical solution for vehicle navigation systems.
Verifying complex continuous real-time systems with coinductive CLP(R)

Timed automata have been used as a powerful formalism for specifying, designing, and analyzing real-time systems. We consider the generalization of timed automata to Pushdown Timed Automata (PTA). We show how PTA can be elegantly modeled via logic programming extended with co-induction and constraints over reals. We propose a general framework based on constraint logic programming and co-induction for modeling/verifying real-time systems. We use this framework to develop an elegant solution to the generalized railroad crossing problem of Lynch and Heitmeyer. Interesting properties of the system can be verified merely by posing appropriate queries.
How to approach neutropenia

Neutropenia is defined as the reduction in the absolute number of neutrophils in the blood circulation. Acute neutropenia is a relatively frequent finding, whereas disorders of production of neutrophils are quite rare. Acute neutropenia is often well tolerated and normalizes rapidly. Neutropenia arising as a result of underlying hematologic disorders is far more significant. Such a patient may be at risk for infectious complications and will likely require a thorough investigation. Acute neutropenia evolves over a few days and occurs when neutrophil use is rapid and production is impaired. Chronic neutropenia may last for 3 months or longer and is a result of reduced production, increased destruction, or excessive splenic sequestration of neutrophils. Neutropenia may be classified by whether it arises secondarily to causes extrinsic to BM myeloid cells, which is common; as an acquired disorder of myeloid progenitor cells, which is less frequent; or as an intrinsic defect arising from impaired proliferation and maturation of myeloid progenitor cells in the BM, which is rare. Severe neutropenia with absolute neutrophil counts below 500/μL increases susceptibility to bacterial or fungal infections. Multiple disorders of severe congenital neutropenia have been found by the discovery of genetic defects affecting differentiation, adhesion, and apoptosis of neutrophil precursors. Elucidation of the multiple genetic defects have provided insight into the biology of the cell involving membrane structures, secretory vesicles, mitochondrial metabolism, ribosome biogenesis, transcriptional regulation, and cytoskeletal dynamics, as well as the risk for myelodysplasia and acute myeloid leukemia.
Blood Product Use by Hemophiliacs in Relation to AIDS Risk Awareness and Patient Variables

Although some hemophiliacs in other studies have reported restricting blood product use because of fear of possible transmission of the human immunodeficiency virus (HIV), no overall change in the quantity of blood products infused between January 1981 through December 1985 was found in a sample of 40 hemophiliacs before or after they became aware of the risk of contracting the acquired immunodeficiency syndrome (AIDS). However, there was a significant linear increase in blood product use with time during the period of AIDS risk awareness. This may be a nonspecific, chance finding: or it may reflect an increase in spontaneous bleeds secondary to AIDS-related stress. The implications of these findings are discussed, and specific areas for future research are recommended.
Observation of two-color ghost imaging

Two-photon quantum imaging has so far demonstrated two peculiar features: (1) reproducing nonlocal images in "ghost" imaging type experiments and (2) improving imaging spatial resolution beyond the classical limit in quantum lithography type measurements. This article reports an experimental study on non-degenerate, two-color, biphoton ghost imaging which reproduced a nonlocal ghost image and simultaneously enhanced the angular resolving power of imaging by means of a greater field of view or by means of a greater imaging amplification compared with that of classical imaging.
A comparison of central aversive stimulation and peripheral shocks in the production of learned helplessness

Rats were given helplessness training with either inescapable peripheral shocks or inescapable, similarly aversive, central stimulation in the dorsal midbrain. The effects of helplessness treatment were assessed in an FR 3 leverpress escape task administered 1 day later. Helplessness treatment with peripheral shocks produced severe deficits in later escape to peripheral shock, but not to dorsal midbrain stimulation. Helplessness treatment with dorsal midbrain stimulation produced no deficits in later escape to either dorsal midbrain stimulation or peripheral shocks. These data pose problems for a strict cognitive model of the helplessness syndrome.
Mutational analysis of the primary substrate specificity pocket of complement factor B. Asp(226) is a major structural determinant for p(1)-Arg binding.

Factor B is a serine protease, which despite its trypsin-like specificity has Asn instead of the typical Asp at the bottom of the S1 pocket (position 189, chymotrypsinogen numbering). Asp residues are present at positions 187 and 226 and either one could conceivably provide the negative charge for binding the P1-Arg of the substrate. Determination of the crystal structure of the factor B serine protease domain has revealed that the side chain of Asp226 is within the S1 pocket, whereas Asp187 is located outside the pocket. To investigate the possible role of these atypical structural features in substrate binding and catalysis, we constructed a panel of mutants of these residues. Replacement of Asp187caused moderate (50–60%) decrease in hemolytic activity, compared with wild type factor B, whereas replacement of Asn189resulted in more profound reductions (71–95%). Substitutions at these two positions did not significantly affect assembly of the alternative pathway C3 convertase. In contrast, elimination of the negative charge from Asp226 completely abrogated hemolytic activity and also affected formation of the C3 convertase. Kinetic analyses of the hydrolysis of a P1-Arg containing thioester by selected mutants confirmed that residue Asp226 is a primary structural determinant for P1-Arg binding and catalysis.
Inhibitors of hepatitis C virus NS3.4A protease. Part 3: P2 proline variants.

Abstract We recently described the identification of an optimized α-ketoamide warhead for our series of HCV NS3·4A inhibitors. We report herein a series of HCV protease inhibitors incorporating 3-alkyl-substituted prolines in P2. These compounds show exceptional enzymatic and cellular potency given their relatively small size. The marked enhancement of activity of these 3-substituted proline derivatives relative to previously reported 4-hydroxyproline derivatives constitutes additional evidence for the importance of the S2 binding pocket as the defining pharmacophore for inhibition of the NS3·4A enzyme.
CHARACTERISTICS OF SEXUAL AND ASEXUAL RESTING CYST (STATOSPORE) FORMATION IN DINOBRYON CYLINDRICUM IMHOF (CHRYSOPHYTA)1

The reproductive significance of siliceous cysts (statospores) produced by the common vernal chrysophyte Dinobryon cylindricum Imhof has been investigated under defined culture conditions. Three types of statospores have thus far been induced in culture: 1) uninucleate, asexual; 2) binucleate, asexual (potentially autogamic); 3) binucleate, sexual (zygotic). The production of each type of cyst responds differently to an array of nutrient deficiencies (P, N, vitamins, micrometals). An individual clone may be capable of participating in the production of all or only a subset of these types of resting cysts. All D. cylindricum statospores are morphologically identical regardless of their reproductive significance. Sexual reproduction leading to zygotic statospore formation is anisogamous, heterothallic, and involves a gametogenic hormone (erogen) that is apparently continuously released from female clones. Only a single bipolar mating group is documented here and clonal compatibility varies considerably within the mating group. The dynamics of encystment for each type of statospore has been determined relative to the growth of the vegetative cell population. Statospores may be produced either during the exponential phase (intrinsic encystment) or stationary phase (extrinsic encystment) of culture growth depending on the clones involved. The effect of both asexual and sexual resting cyst production on the net growth rate and dynamics of natural chrysophyte populations is discussed. Statospores appear to represent a more flexible reproductive strategy than the resistant zygospores produced by the other common groups of planktonic microalgae.
Product take-back: sensors-based approach

The driving forces behind product take-back and green manufacturing are well established. The two main product end-of-life options are reuse/remanufacturing and recycling. For either option, all take-back units are treated equally because no information that tracks the conditions of a product during its useful life is available. For example, all expired PCs are treated equally; no distinction can be made about which units still have healthy hard disks. This paper discusses sensor-based monitoring and prognostic methodologies for tracking the condition of products while being used by customers and timely and targeted servicing, smart and selective disassembling and refurbishing of products with known (long) remaining lives. The paper also discusses the added benefits to product manufacturers when the time comes to redesign their products. The real-time field data on service and utilization of products are communicated to manufacturers’ headquarters for further analysis.
Novel targets for treating heart and muscle disease – stabilizing ryanodine receptors and preventing intracellular calcium leak

Ryanodine receptors (RyRs) function as intracellular Ca(2+) release channels on the endoplasmic and sarcoplasmic reticulum membranes. In striated muscles, Ca(2+) release through RyRs controls muscle excitation-contraction coupling. RyR channel function is regulated by a cytoplasmic scaffold domain that forms a macromolecular signaling complex including calstabin (formerly known as FK506-binding protein), calmodulin, phosphodiesterase, kinase and phosphatase proteins. An increasing number of genetic and acquired diseases has been associated with intracellular Ca(2+) leak. In heart failure, for instance, the RyR complex becomes altered, resulting in chronic channel dysfunction and chronic sarcoplasmic reticulum Ca(2+) leak. Recently, the efficacy of novel Ca(2+) release channel-stabilizing drugs has been demonstrated in cardiac and skeletal muscle disease models.
Real-time optimization of distribution system considering interaction between markets

In this paper a novel architecture for real-time optimization is proposed based on Receding Horizon Control (RHC). The proposed architecture is capable of including real-time system data and can incorporate uncertainties in resources and market price.The main focus is to interface an active distribution network to wholesale market and neighboring Distribution System Companies (DISCOs) incorporating real-time price prediction. The effectiveness of proposed method is examined on a modified 32-bus distribution network incorporating Distributed Generators (DGs) such as wind and storage, neighboring DISCOs and wholesale market entities. It has been observed that the proposed method outperforms conventional methods and has the potential to implement dynamic stochastic optimal power distribution in modern power grid.
Virtual interpersonal touch: Haptic interaction and copresence in collaborative virtual environments

As digital communication becomes more commonplace and sensory rich, understanding the manner in which people interact with one another is crucial. In the current study, we examined the manners in which people touch digital representations of people, and compared those behaviors to the manner in which they touch digital representations of nonhuman objects. Results demonstrated that people used less force when touching people than other nonhuman objects, and that people touched the face with less force than the torso area. Finally, male digital representations were touched with more force than female representations by subjects of both genders. We discuss the implications of these data to the development of haptic communication systems as well as for a methodology of measuring the amount of copresence in virtual environments.