cssi/SciSciGPT-SciSciNet huggingface dataset:
Lipid Catabolism of Relapsing Fever Borreliae

Relapsing fever borreliae require lipid compounds for growth in vitro. In this study, the major pathways of lipid catabolism in three species of tick-borne relapsing fever borreliae were investigated. Thin-layer chromatography was used to compare chloroform-methanol extracts of fresh culture media with extracts of exhausted culture media after organisms were removed by centrifugation. The chromatographic data demonstrated that lysolecithin was removed from the culture media during growth of the spirochetes, whereas lecithin, sphingomyelin, triglycerides, and cholesterol esters were not affected by growth of the organisms. Sonic extracts of the organism were tested for the presence of specific enzymes of lipid catabolism. Lysolecithinase, glycerophosphorylcholine diesterase, and acid phosphatase activities were demonstrated. Thus, these organisms can sequentially dissimilate lysolecithin to fatty acids, choline, inorganic phosphate, and glycerol. Assays for phospholipases A, C, and D, α-glycerophosphate dehydrogenase, alkaline phosphatase, and lipase were negative. Images
Impacts of Global Transcriptional Regulators on Persister Metabolism

Bacterial persisters are phenotypic variants with an extraordinary capacity to tolerate antibiotics, and they are hypothesized to be a main cause of chronic and relapsing infections. Recent evidence has suggested that the metabolism of persisters can be targeted to develop therapeutic countermeasures; however, knowledge of persister metabolism remains limited due to difficulties associated with isolating these rare and transient phenotypic variants. By using a technique to measure persister catabolic activity, which is based on the ability of metabolites to enable aminoglycoside (AG) killing of persisters, we investigated the role of seven global transcriptional regulators (ArcA, Cra, cyclic AMP [cAMP] receptor protein [CRP], DksA, FNR, Lrp, and RpoS) on persister metabolism. We found that removal of CRP resulted in a loss of AG potentiation in persisters for all metabolites tested. These results highlight a central role for cAMP/CRP in persister metabolism, as its perturbation can significantly diminish the metabolic capabilities of persisters and effectively eliminate the ability of AGs to eradicate these troublesome bacteria.
Practical issues in ultrashort-laser-pulse measurement using frequency-resolved optical gating

We explore several practical experimental issues in measuring ultrashort laser pulses using the technique of frequency-resolved optical gating (FROG). We present a simple method for checking the consistency of experimentally measured FROG data with the independently measured spectrum and autocorrelation of the pulse. This method is a powerful way of discovering systematic errors in FROG experiments. We show how to determine the optimum sampling rate for FROG and show that this satisfies the Nyquist criterion for the laser pulse. We explore the low- and high-power limits to FROG and determine that femtojoule operation should be possible, while the effects of self-phase modulation limit the highest signal efficiency in FROG to 1%. We also show quantitatively that the temporal blurring due to a finite-thickness medium in single-shot geometries does not strongly limit the FROG technique. We explore the limiting time-bandwidth values that can be represented on a FROG trace of a given size. Finally, we report on a new measure of the FROG error that improves convergence in the presence of noise.
Variable presentation between a mother and a fetus with Goltz syndrome.

Focal dermal hypoplasia, also known as Goltz-Gorlin syndrome,(OMIM 305600) is a congenital disorder affecting tissues derivedfrom mesoderm and ectoderm. Common presenting featuresinclude atrophic skin, aplasia cutis, fat nodules in the dermis,and skin pigment changes. Nails are often dysplastic and hairsparse. More severe anomalies may include anophthalmia/microphthalmia, cleft lip and palate, and limb anomaliesincluding amelia, abdominal wal l defects, renal malformations,and diaphragmatic hernia. Patien ts are often symmetrically smallwith microcephalyandsomehaveintellectualdisability;however,central nervous system involv ement is not a typical feature.
Retrospective evaluation of measles antibody titers in vaccinated captive gorillas (Gorilla gorilla gorilla)

Retrospective analyses of banked serum samples and medical records from captive western lowland gorillas (Gorilla gorilla gorilla) at Lincoln Park Zoo showed that vaccination of gorillas with a human vaccine induced antibody production. No significant relationship was found between the groups that received one, two, or three vaccinations and the probability of seroconversion. These data also suggested that antibodies in western lowland gorillas persist for at least 11 yr. This information is useful in the assessment of vaccination protocols for captive gorillas and in the implementation of preventive care in wild gorilla populations.
Neural models for transistor and mixed-level test generation

We derive new neural network models for n and pFET transistors for use in switch-level test generation. Special characteristics included in the model are bidirectionality and an explicit representation of the substrate. We prove the optimality of these models. The results for an example CMOS circuit indicate that modeling circuit portions at the switch-level allows more accurate tests for transistor stuck-open faults without giving up the speed of gate-level ATPG. >
The Organizational Chart: The Manager's Toy

(1982). The Organizational Chart: The Manager's Toy. Journal of Physical Education, Recreation & Dance: Vol. 53, Including Leisure Today, pp. 47-48.
Using the Specialization Framework to Determine Degree of Dietary Specialization in a Herbivorous Woodrat

To be considered a dietary specialist, mammalian herbivores must consume large quantities of a plant species considered "difficult" with respect to nutrient or toxin content, and possess specialized adaptations to deal with plant defensive compounds or low nutritional content. Populations of Neotoma lepida in the Great Basin consume Juniperus osteosperma, a plant heavily defended by terpenes, but a detailed dietary analysis of this population is lacking. Therefore, we investigated the extent of dietary specialization in this species in comparison with the better-studied specialist species, N. stephensi. Microhistological analysis of feces from N. lepida revealed that greater than 90% of their diet in nature was comprised of juniper. In laboratory tolerance trials, N. lepida tolerated a diet of 80% J. osteosperma, similar to that observed for N. stephensi. There was no difference in the abilities of N. lepida and N. stephensi to metabolize hexobarbital, a proxy compound for terpene metabolism. In preference tests of native and non-native juniper species, N. lepida did not exhibit a preference for its native or co-occurring juniper, J. osteosperma, over the non-native species, J. monosperma, whereas N. stephensi preferred its native or co-occurring juniper J. monosperma over non-native J. osteosperma. Behavioral and habitat differences between these woodrat species lead to the categorization of N. stephensi as an obligate juniper specialist with a small range that overlaps that of its preferred food, J. monosperma, and N. lepida as a facultative juniper specialist with a large range, and only a portion of its distribution containing populations that feed extensively on J. osteosperma.
Training and Recruitment of Agricultural Economic Personnel: II. The Civil Servant

O NE of the most encouraging things about recruitment and training is that the experts are realizing the lack of any definite program and are trying to do something about it as rapidly as possible, even though they are becomingly modest about any scientific standards.' I am not an expert in this field and can only offer a few observations and general suggestions which occur to me after about a dozen years in the Government service, during which I have been hired a few times and have hired and supervised a few other people. First, I hope the editor will let me waste a little space to wish we could find a better word than "recruitment." Rightly or wrongly the word always suggests to me the posters, pep talks, brass bands, and parades which are used to induce young men to join the army. We need an entirely different program for hiring agricultural economists. There should be two main parts to such a program. 1. The various kinds of work in the field should be described as completely and as honestly as possible so that a young man can apply for the kind of work for which he is best suited. Young college graduates usually do not realize the wide variety of work in the Government, and are inclined to make many unwarranted generalizations. My own experience has been with research on matters of agricultural policy-particularly in the field of marketing. I can truthfully report that in this kind of work I have never been greatly bothered with routine and red tape; have had as much academic freedom as I would expect in most places; and have had plenty of chance for personal recognition. These observations might not be so true of some other kinds of Government work. 2. Some better way needs to be found to put applicants on the registers for which they are best qualified and to rank them in order of their ability. This is not easy to do. My only specific suggestion is that greater weight should be given to personal inter-
Germinal cell aplasia: response of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone to LH/FSH-releasing hormone with histopathologic correlation.

Five male patients with infertility due to biopsy-proven germinal cell aplasia were given a 100-μg bolus of luteinizing hormone (LH)/follicle-stimulating hormone (FSH)-releasing hormone (LRH), and the resultant LH, FSH, and testosterone responses were correlated with their histologic patterns on testicular biopsy. The basal and stimulated FSH values were elevated in four of five patients. Basal LH values were elevated in three patients, while two clearly had exaggerated LH and testosterone responses to LRH. Although there was little correlation between various parameters, elevated basal LH values were associated with Leydig cell hyperplasia. Higher basal FSH levels were present when fibrosis and complete aplasia of germinal elements were found in the same biopsy specimen, and the magnitude of the FSH response to LRH correlated positively with the basal concentration. The findings of elevated basal LH values, an exaggerated LH response to LRH, lack of testosterone response, and Leydig cell hyerplasia indicate a definite disturbance of the LH-testosterone axis in many patients with germinal cell aplasia. Therefore, the regulation of secretion of both gonadotropins appears to be abnormal in this disorder.
Listener estimations of talker age: A meta-analysis of the literature

Numerous studies, most of them cross-sectional studies using one sample per talker, have demonstrated that listeners make relatively accurate age judgments from hearing talkers' voices. The current study analyzed the results of several such direct age estimation studies to characterize better the perception of talker age over a larger number of individuals. A review of the direct age estimation literature was performed. Data sets from seven papers were reconstituted, and an analysis of the combined data (meta-analysis) including 530 data points was conducted. The reconstituted and combined data included talkers aged 10-90. Listeners appeared to overestimate age when talkers were younger and to underestimate it when talkers were older.
Constitutional Purgatory: Shades and Presences Inside the Courtroom

The Sixth Amendment confrontation clause requires the presence at trial of witnesses in criminal cases. Absent a compelling countervailing interest, such as safeguarding the emotional well-being and testimonial capacity of a child witness, distant testifying (by way of a live, closed-circuit two-way television transmission, say) is impermissible. Neither convenience nor mere necessity is enough to justify diminishing the defendant’s right to face to face confrontation. But what makes such images insufficient for purposes of confrontation? How much presence must a video provide to avoid casting a witness into “constitutional purgatory?” This query, paraphrasing a recent federal court opinion, serves as a springboard to a larger issue: How much presence ought visual images in general provide as authority for the legal judgments they help to produce? Addressing this larger question is part of the challenge of visualizing law in the digital age.
A Derivation of the Equation for a Vibrating String

(1957). A Derivation of the Equation for a Vibrating String. The American Mathematical Monthly: Vol. 64, No. 3, pp. 155-157.
In vitro cell-mediated immunity of cerebrospinal-fluid lymphocytes to myelin basic protein in primary demyelinating diseases.

Abstract In an attempt to characterize the immunologic reactivity of cerebrospinal-fluid lymphocytes in demyelinating diseases, we compared the myelin-basic-protein-induced in vitro responses of these cells to peripheral blood lymphocytes from the same subjects with a variety of neurologic diseases. Peripheral blood lymphocytes from patients with acute disseminated encephalomyelitis and progressive multiple sclerosis had increased reactivity as compared to those of normal volunteers (P<0.01 and P<0.05, respectively). Cerebrospinal-fluid lymphocytes from patients with acute disseminated encephalomyelitis and acute and progressive (but not stable) multiple sclerosis were more reactive than cells from subjects with other neurologic diseases (P<0.005, P<0.02 and P<0.05, respectively). Cerebrospinal-fluid lymphocytes manifested a greater reactivity than peripheral blood lymphocytes in acute and progressive multiple sclerosis but not in acute disseminated encephalomyelitis. These findings demonstrate that lymph...
Whole animal physiology redux

even though i retired completely in 1998 and vowed never to attend another meeting, I had to renege because it is such a great honor to be invited to give this lecture honoring my mentor, Julius Comroe. I thank the selection committee for considering me. Of the nine scientists chosen since this
Analysis on Status of Supply and Demand of Occupational Health Services in Deyang

Objective Deyang has large number of factories and mines which reguire occupational health services,and occupational health service capacity is directly related to the ability to meet the demand. In order to understand differences between the supply and demand,the survey was conducted.Methods Unified questionnaire was used to make an investigatie the enterprises and occupational health service institution in Deyang.Results After investigation,the detection coverage of occupational health unit was 3.8%,the detection rate of occupational risk factors was 11.7%,the coverage of occupational health medical units was 6.4%,the occupational physical examination rate was 14.4%,the conduction rate of occupational hazards evaluation of construction projects was 2.1%. By contrast,the amounts of occupational health service unit was 50% averagely far its capaclty . Conclusion This great gap between the demand and the supply in this field need to be mininized by improve the occupational health service capacity in deyang.
431 MULTIPOTENT ADULT PROGENITOR CELLS CAN RECONSTITUTE LYMPHOHEMATOPOIETIC LINEAGES AND CONTRIBUTE TO NONHEMATOPOIETIC SYSTEMS IN IRRADIATED IMMUNODEFICIENT MICE.

Multipotent adult progenitor cells (MAPCs) are rare cells that have been identified within human and rodent bone marrow (BM) that can differentiate into mesodermal, endodermal, and ectodermal lineages in vitro. High O2 (20%) MAPCs also differentiate into hematopoietic stem cells (HSC) in vivo in NOD/SCID mice with very low engraftment levels. Since the initial description of MAPCs, we modified our culture conditions to isolate MAPCs under 5% O2 conditions, resulting in MAPCs with higher mRNA and protein levels of the ES-transcription factor, Oct4, and greater in vitro differentiation potential. We investigated the hematopoietic and nonhematopoietic engraftment levels of eGFP/CD45.2 transgenic C57Bl/6 MAPCs in NOD/SCID (CD45.1 positive) mice irradiated with 275cGy and treated with anti-asialo GM1 antibody (Ab) on days 1, 11, and 22 following transplantation. When 106 MAPCs were transplanted, up to 70% GFP/CD45.2 cells were present in peripheral blood (PB), BM, and spleen at 13 weeks post-transfer. Lymph nodes and Peyer9s patches also contained GFP+ cells. FACS analysis of cells from spleen, BM, and PB revealed multilineage engraftment with differentiation to myeloid, B, and T-lymphoid cells. We detected eGFP+ cells co-expressing Sca1+/cKit+ or Thy1+/cKit+, suggesting generation of HSCs from MAPCs, consistent with the finding that GFP+ CFU-Mix, BFU-E, and CFU-GM were present. eGFP+ splenic T cells were capable of reacting to Balb/C-derived cells and to stimulation by anti-CD3+anti-CD28 monoclonal Abs. We measured the percentage of GFP using real-time PCR and detected its presence in lung, liver, intestine, kidney, stomach, and spleen as early as 3 weeks following transplantation, pancreas as early as 6 weeks, and skin as early as 12 weeks. In conclusion, MAPCs isolated in 5% O2 conditions and grafted in the presence of anti-NK Abs engraft in lymphohematopoietic and some nonhematopoietic organs to a significantly greater extent than was previously demonstrated. Thus, MAPCs may be an alternative source of HSCs to treat congenital or acquired hematopoietic disorders or to establish chimerism prior to using the same cells to treat disorders amenable to MAPC-derived therapies.
Cross-cultural considerations in custody and parenting plans

Children are entitled to their cultural heritage and it is important to their development. Cultural considerations must be incorporated in devising custody and parenting plans. Several generalizations are useful. Children are capable of integrating highly diverse and even contradictory cultural and religious identity fragments. The more distinctly a child's cultural inheritance varies from that of the dominant society, the more it must be taken into account. The more bias or hostility that exists against an aspect of the child's cultural inheritance, the more that cultural component is to be considered. The value of culture to the child is best seen in a developmental context. We are limited in our ability to ensure children's rights to cultural inheritance by our own ethnocentrism or ignorance, by bureaucratic or legalistic definitions of cultural identity, by the desire of one parent to reduce the contribution of the other parent, and by a tendency to rely on consistency as a value in and of itself.
Ct2 Bladder Cancer

The patient is an 80-year-old man who presented with gross hematuria. His past medical history indicates he was a cigarette smoker with 50 pack/years. He was successfully treated for carcinoma of the lung 7 years ago. He received chemotherapy, radiation, and surgery. He has mild COPD but has a good performance status. His laboratory studies do not indicate any abnormalities in terms of renal function. He does not have any significant cardiac disease. He has a medium build. He had prostate cancer and underwent a successful radical prostatectomy 10 years ago. His PSA is undetectable. He has some urinary incontinence and wears two pads/day. He underwent the appropriate investigations for gross hematuria. A CT scan of the abdomen and pelvis was normal with the exception of a 4-cm posterior mass in the bladder. There was no hydronephrosis and no enlarged lymph nodes. He underwent a transurethral resection of a solitary bladder tumor performed by another urologist. The tumor was described as large and sessile. It was located on the posterior wall and was approximately 4 cm. The bimanual examination did not reveal a mass. The pathology report stated that the tumor was a high-grade urothelial carcinoma with invasion into the muscularis propria. There was no lymphovascular invasion. I performed a reTURBT, and at that procedure, I did not identify any obvious tumor but the prior resection site was evident. I resected the prior tumor site quite extensively both in depth and width. The pathology revealed only focal carcinoma in situ. There was ample muscle in the specimen and there was some fat as well. As stated, they were free of any cancer. The patient is receptive to any treatment approach.
The role of national champions in the evolving footprint of vehicle production in Europe - 1990-2013

By the mid-80s, industry leaders and policy makers in Europe were very concerned about the looming threat from Asian vehicle producers. Yet, 30 years later, the share of European vehicle production represented by producers headquartered in Europe remains large. This paper discusses the continued success of European-based producers in the context of the changing footprint of vehicle production in Europe. How did the national champions adjust to the introduction of the common market and the enlargement of Europe? What differences and similarities can be identified in their regional investment strategies?
Analytical bond-order potential for the cadmium telluride binary system

CdTe and Cd${}_{1\ensuremath{-}x}$Zn${}_{x}$Te are the leading semiconductor compounds for both photovoltaic and radiation detection applications. The performance of these materials is sensitive to the presence of atomic-scale defects in the structures. To enable accurate studies of these defects using modern atomistic simulation technologies, we have developed a high-fidelity analytical bond-order potential for the CdTe system. This potential incorporates primary ($\ensuremath{\sigma}$) and secondary ($\ensuremath{\pi}$) bonding and the valence dependence of the heteroatom interactions. The functional forms of the potential are directly derived from quantum-mechanical tight-binding theory under the condition that the first two and first four levels of the expanded Green's function for the $\ensuremath{\sigma}$- and $\ensuremath{\pi}$-bond orders, respectively, are retained. The potential parameters are optimized using iteration cycles that include first-fitting properties of a variety of elemental and compound configurations (with coordination varying from 1 to 12) including small clusters, bulk lattices, defects, and surfaces, and then checking crystalline growth through vapor deposition simulations. It is demonstrated that this CdTe bond-order potential gives structural and property trends close to those seen in experiments and quantum-mechanical calculations and provides a good description of melting temperature, defect characteristics, and surface reconstructions of the CdTe compound. Most importantly, this potential captures the crystalline growth of the ground-state structures for Cd, Te, and CdTe phases in vapor deposition simulations.
Differences in Routine Laboratory Ordering Between a Teaching Service and a Hospitalist Service at a Single Academic Medical Center.

OBJECTIVES Studies have shown that the overutilization of laboratory tests ("labs") for hospitalized patients is common and can cause adverse health outcomes. Our objective was to compare the ordering tendencies for routine complete blood counts (CBC) and chemistry panels by internal medicine residents and hospitalists. METHODS This observational study included a survey of medicine residents and hospitalists and a retrospective analysis of labs ordering data. The retrospective data analysis comprised patients admitted to either the teaching service or nonteaching hospitalist service at a single hospital during 2014. The survey asked residents and hospitalists about their practices and preferences on labs ordering. The frequency and timing of one-time and daily CBC and basic chemistry panel ordering for teaching service and hospitalist patients were obtained from our data warehouse. The average number of CBCs per patient per day and chemistry panels per patient per day was calculated for both services and multivariate regression was performed to control for patient characteristics. RESULTS Forty-four of 120 (37%) residents and 41 of 53 (77%) hospitalists responded to the survey. Forty-four (100%) residents reported ordering a daily CBC and chemistry panel rather than one-time labs at patient admission compared with 22 (54%) hospitalists (P < 0.001). For CBCs, teaching service patients averaged 1.72/day and hospitalist service patients averaged 1.43/day (P < 0.001). For basic chemistry panels, teaching service patients averaged 1.96/day and hospitalist service patients averaged 1.78/day (P < 0.001). Results were similar in multivariate regression models adjusting for patient characteristics. CONCLUSIONS Residents' self-reported and actual use of CBCs and chemistry panels is significantly higher than that of hospitalists in the same hospital. Our results reveal an opportunity for greater supervision and improved instruction of cost-conscious ordering practices.
Maximum Magnitude Estimation for An Intraplate Setting - Example: The Giles County, Virginia, Seismic Zone

The process of maximum magnitude estimation is intrinsically subjective and depends directly on the experience and judgment of the analyst. Coppersmith et al. (1987; Table 1) discuss six methods for determining the maximum magnitude earthquake for a seismogenic zone. Those include: (I) Addition of an increment to the largest historical earthquake, (II) Extrapolation of magnitude recurrence relations, (III) Use of source dimensions to estimate magnitude, (IV) Statistical approaches (application of extreme value theory and maximum likelihood techniques), (V) Strain rate or moment release rate methods, and (VI) Reference to a global data base. Each technique has associated uncertainties in its applicability to the zone under consideration as well as in the specification of the key parameters involved. Of the six techniques listed above, only the first three are applicable to the data bases presently available for intraplate areas. Application of methods I, II, and III, to the Giles County, Virginia, seismic zone leads to the following results: M S,I = 6.9 (second subscript indicating which of the six methods was used) from adding a 1.0 increment to the maximum historical earthquake known to have occurred in the zone (May 31, 1897; MMI = VIII; m b = 5.8, M S = 5.9), M S,II = 7.0 from extension of the magnitude recurrence curve for the zone to a recurrence interval of 1000 years, and M S,III = 6.5 from the average of six estimates for the fault zone area. For a single estimate of maximum magnitude, the average of the above three values M S = 6.8 or equivalently, m b = 6.3 can be used.
Review: The Donatist Schism. Controversy and Contexts, edited by Richard Miles

Richard Miles, ed. The Donatist Schism. Controversy and Contexts . Translated Texts for Historians, Contexts 2. Liverpool: Liverpool University Press, 2016. 394 pp. xi. ISBN: 9781781382813. $120.00. For half a century after its publication, in 1952, William Frend's The Donatist Church: A Movement of Protest in Roman North Africa remained the standard narrative on the late antique North African Christian controversy. Among the explosion of recent scholarship on late antique North Africa and the Donatist Schism in particular, Brent Shaw's monumental and magisterial Sacred Violence. African Christians and Sectarian Hatred in the Age of Augustine (2011) has had the most significant impact on revising Frend's traditional narrative. The book currently under review, itself revisionist, challenges several fundamental assumptions about the Donatist conflict, and its impressive roster of scholars systematically engages with Sacred Violence throughout, challenging its argument in numerous instances. This outstanding and important collection of studies is therefore an appropriate tribute to Brent Shaw, to whom it is suitably dedicated. Based on a 2014 conference held in Sydney, the volume includes fifteen chapters, three of them introductory, followed by twelve studies on a specific topic or theme of relevance to the Donatist Schism; there is also an excellent Bibliography and a useful Index. Following a general introduction by the volume's editor, Richard Miles (“The Donatist Controversy: Parallel Histories, Multiple Narratives”), John Whitehouse presents an overview of events (“The Course of the Donatist Schism in Late Roman North Africa”) as well as of its main scholarly interpretations (“The Scholarship of the Donatist Controversy”) which concludes with a list of “Key Themes for Future Research” (49–53). Both of Whitehouse's chapters are useful introductions to the topic, particularly for students and readers unfamiliar with the details of this religious controversy, and especially considering that the following chapters mainly address readers familiar with the topic. In addition to outlining the key historical moments of this controversy and its scholarship, Whitehouse introduces key vocabulary and concepts, surveys the main sources, and …
Effect of the Earned Income Tax Credit on Hospital Admissions for Pediatric Abusive Head Trauma, 1995-2013:

Objectives:Policies that increase household income, such as the earned income tax credit (EITC), have shown reductions on risk factors for child maltreatment (ie, poverty, maternal stress, depressi...
Dynamics and control of a quadrotor with a payload suspended through an elastic cable

We study the problem of a quadrotor transporting a payload suspended through a cable. While prior work has modeled the cable as a massless rigid link, in this paper, we consider the cable to be elastic with both spring stiffness and damping. We derive a coordinate-free dynamical model of the system. We use singular-perturbations to show that a geometric controller developed for the case of an inelastic cable still works for the case of an elastic cable to achieve almost global exponential tracking of a desired load position to within a certain bound. We provide numerical results to validate the proposed controller for various spring and damping coefficients for the cable.
Mn 2+ -ZnSe/ZnS@SiO₂ Nanoparticles for Turn-on Luminescence Thiol Detection.

Biological thiols are antioxidants essential for the prevention of disease. For example, low levels of the tripeptide glutathione are associated with heart disease, cancer, and dementia. Mn2+-doped wide bandgap semiconductor nanocrystals exhibit luminescence and magnetic properties that make them attractive for bimodal imaging. We found that these nanocrystals and silica-encapsulated nanoparticle derivatives exhibit enhanced luminescence in the presence of thiols in both organic solvent and aqueous solution. The key to using these nanocrystals as sensors is control over their surfaces. The addition of a ZnS barrier layer or shell produces more stable nanocrystals that are isolated from their surroundings, and luminescence enhancement is only observed with thinner, intermediate shells. Tunability is demonstrated with dodecanethiol and sensitivities decrease with thin, medium, and thick shells. Turn-on nanoprobe luminescence is also generated by several biological thiols, including glutathione, N-acetylcysteine, cysteine, and dithiothreitol. Nanoparticles prepared with different ZnS shell thicknesses demonstrated varying sensitivity to glutathione, which allows for the tuning of particle sensitivity without optimization. The small photoluminescence response to control amino acids and salts indicates selectivity for thiols. Preliminary magnetic measurements highlight the challenge of optimizing sensors for different imaging modalities. In this work, we assess the prospects of using these nanoparticles as luminescent turn-on thiol sensors and for MRI.
Radiotherapy enhances natural killer cell cytotoxicity and localization in pre-clinical canine sarcomas and first-in-dog clinical trial

We have previously shown that radiotherapy (RT) augments natural killer (NK) functions in pre-clinical models of human and mouse cancers, including sarcomas. Since dogs are an excellent outbred model for immunotherapy studies, we sought to assess RT plus local autologous NK transfer in canine sarcomas. Dog NK cells (CD5dim, NKp46+) were isolated from PBMCs and expanded with irradiated K562-C9-mIL21 feeder cells and 100 IU/mL recombinant human IL-2. NK homing and cytotoxicity ± RT were evaluated using canine osteosarcoma tumor lines and dog patient-derived xenografts (PDX). In a first-in-dog clinical trial for spontaneous osteosarcoma, we evaluated RT and intra-tumoral autologous NK transfer. After 14 days, mean NK expansion and yield were 19.0-fold (±8.6) and 258.9(±76.1) ×106 cells, respectively. Post-RT, NK cytotoxicity increased in a dose-dependent fashion in vitro reaching ~ 80% at effector:target ratios of ≥10:1 (P < 0.001). In dog PDX models, allogeneic NK cells were cytotoxic in ex vivo killing assays and produced significant PDX tumor growth delay (P < 0.01) in vivo. After focal RT and intravenous NK transfer, we also observed significantly increased NK homing to tumors in vivo. Of 10 dogs with spontaneous osteosarcoma treated with focal RT and autologous NK transfer, 5 remain metastasis-free at the 6-month primary endpoint with resolution of suspicious pulmonary nodules in one patient. We also observed increased activation of circulating NK cells after treatment and persistence of labelled NK cells in vivo. NK cell homing and cytotoxicity are increased following RT in canine models of sarcoma. Results from a first-in-dog clinical trial are promising, including possible abscopal effects.
Retrospective Evaluation of Clinical Experience With Intravenous Ascorbic Acid in Patients With Cancer

Background. Intravenous ascorbic acid (IV AA) has been used extensively in cancer patients throughout the United States. Currently, there are limited data on the safety and clinical effects of IV A...
Immunotherapy of Primary Brain Tumors: Facts and Hopes

The field of cancer immunotherapy has made exciting progress for some cancer types in recent years. However, recent failures of late-phase clinical trials evaluating checkpoint blockade in patients with glioblastoma (GBM) represent continued challenges for brain cancer immunotherapy. This is likely due to multiple factors including but not limited to marked genetic and antigenic heterogeneity, relatively low mutational loads, and paucity of GBM-infiltrating T cells. We review recent and ongoing studies targeting the checkpoint molecules as monotherapy or in combination with other modalities, and discuss the mechanisms underlying the unresponsiveness of GBM to single-modality immunotherapy approaches. We also discuss other novel immunotherapy approaches that may promote T-cell responses and overcome the “cold tumor” status of GBM, including oncolytic viruses and adoptive T-cell therapy. Clin Cancer Res; 24(21); 5198–205. ©2018 AACR.
Genetik primärer Kopfschmerzen

Die Migrane hat eine erhebliche genetische Komponente. Klassischer Vertreter monogener Migraneformen ist die familiare hemiplegische Migrane, fur die bisher 3 ursachliche, von Mutationen betroffene Gene identifiziert wurden; Arbeiten an transgenen Tiermodellen haben entscheidend zu einem besseren Verstandnis der molekularen Pathophysiologie dieser monogenen Modellerkrankung, aber auch der Migrane insgesamt beigetragen. Daneben existieren auch andere (seltenere) monogene Migrane-Formen, z. B. im Rahmen hereditarer meist vaskularer Syndrome, wie z. B. CADASIL. Auf der anderen Seite stehen die haufigen Migraneformen, die genetisch komplex sind. In diesem Bereich wurden in den letzten wenigen Jahren durch grose genomweite Assoziationsstudien die ersten robusten genetischen Risikofaktoren identifiziert, wobei sich das Feld dynamisch weiterentwickelt. Die vorliegende Uberblicksarbeit stellt den aktuellen Wissensstand zur Migranegenetik dar; Schwerpunkte bilden die Themen hemiplegische Migrane und die jungsten Ergebnisse zu den haufigen Migraneformen. Als Ausblick werden auch praliminare Befunde zur Genetik anderer primarer Kopfschmerzerkrankungen wie Clusterkopfschmerz oder Spannungskopfschmerz besprochen.
Simultaneous Assessment of Transcriptomic Variability and Tissue Effects in the Normal Mouse

We consider two linear mixed models for the normal mouse data [Pritchard et al., 2001]. One models the log 2 intensity measurements directly and the other models the log2 ratios. In each approach, we treat a mouse as a fixed effect, and alternatively, we also model it as a random effect to assess its variability directly. We compare the results from these mixed model approaches. The models agree that array variance is much larger than other sources of variability, but differ somewhat in their lists of genes exhibiting the most significant mouse effects. Under a Bonferroni criterion, the ratio-based model we consider produces more genes with significant mouse effects than the intensity-based model, but fewer genes with significant tissue effects. Both models demonstrate a general statistical framework for concurrently estimating sources of variability and assessing their significance.
IMPROVE A LEARNER: A SURVEY OF TRANSFER LEARNING

Transfer learning is a subclass of machine learning, which uses training data (source), drawn from a diverse domain than that of the testing data (target). The real world is messy and contains an infinite range of novel eventualities. Transfer learning across different feature spaces is usually a tougher problem than Transfer Learning within the common feature space. This survey paper defines transfer learning to feature representation that maps the target domain to the source domains exploiting a set of meticulously manufactured features and applications to transfer learning. This paper systematically examines a feature based transfer techniques and reviews some current analysis on the topic of negative transfer.
Rituximab, lenalidomide, and ibrutinib alone and combined with dose adjusted chemotherapy for patients with high risk diffuse large B-cell lymphoma.

TPS7575Background: Diffuse large B-cell Lymphoma (DLBCL), the most common lymphoid malignancy, is categorized by the putative cell of origin (COO) classification system into germinal center (GCB) a...
DNase-seq to Study Chromatin Accessibility in Early Xenopus tropicalis Embryos

Transcriptional regulatory elements are typically found in relatively nucleosome-free genomic regions, often referred to as "open chromatin." Deoxyribonuclease I (DNase I) can digest nucleosome-depleted DNA (presumably bound by transcription factors), but DNA in nucleosomes or higher-order chromatin fibers is less accessible to the nuclease. The DNase-seq method uses high-throughput sequencing to permit the interrogation of DNase hypersensitive sites (DHSs) across the entire genome and does not require prior knowledge of histone modifications, transcription factor binding sites, or high quality antibodies to identify potentially active regions of chromatin. Here, discontinuous iodixanol gradients are used as a gentle preparation of the nuclei from Xenopus embryos. Short DNase I digestion times are followed by size selection of digested genomic DNA, yielding DHS fragments. These DNA fragments are subjected to real-time quantitative polymerase chain reaction (qPCR) and sequencing library construction. A library generation method and pipeline for analyzing DNase-seq data are also described.
Fatigue analysis and experiment of leaf-spring pivots for high precision flexural static balancing instruments

Abstract For distributed-compliance flexure mechanisms, their service life is affected by fluctuating stress which may result in fatigue failure, but only static failure was taken into consideration in most studies. As one of the best-known types of distributed-compliance flexural pivots, the cross-spring pivot applied to the flexural static balancing instruments is subjected to large enough vertical loads and fluctuating stresses. In this paper, the cross-spring pivot is taken to explore the methods of prolonging its fatigue life, and the methods can be extended to the other pivots based on leaf-springs. Meanwhile, another important performance of the pivot-the rotational stiffness remains unchanged. Firstly, in order to develop a stress-life model, the equivalent fatigue stresses of the cross-spring pivots are derived in which the stress concentration factors are obtained by fitting the finite element results. Then, two methods for prolonging the fatigue life of the pivot are proposed, i.e., increasing the ratio of length to thickness of leaf-springs and reducing stress concentration. To verify the theoretical analysis, the fatigue life of five cross-spring pivots with the same rotational stiffness is tested based on a developed fatigue test bench. Experimental results show that the fatigue life of the cross-spring pivot can be prolonged, which verifies the validity of the two methods.
Using jupyter notebooks to learn high-performance computing

High performance computing (HPC) opens the door to large scale data analysis, computational science, and research computing. To interactively guide undergraduate students through the basics of HPC, we created an open-access course using Jupyter notebooks. We provide the most important concepts for a foundational understanding of HPC. Computational notebooks combine - in a single document - text, and live code, output and visualizations. This paper describes our notebooks, as well as results from student surveys.
Images and Human Rights

This chapter surveys the interplay between images and human rights, focusing on how the interaction among technologies, platforms and agents may alter contemporary human rights practices. It stems from the recognition that images are no longer merely an illustration on the side or just a vehicle for advocacy; they have become a critical evidentiary tool and a mode of information relay on their own terms as well. The chapter thus looks at how the capacity to include images—strongly defined, increasingly tested for impact—has been harnessed in ways that might alter discourses, might privilege some players over others, might present different ethical issues, and might make, in general, a more powerful role for human rights and the greater achievement of long-desired objectives.
Synthesis of macrocyclic polyethers with partially fluorinated side arms

Different types of macrocyclic polyethers with partially fluorinated side arms are prepared. These new macrocyclic ligands are based on sym-dibenzo-16-crown-5 and sym-dicyclohexano-16-crown-5 scaffolds.
Plasma Metabolomic Markers of Insulin Resistance and Diabetes and Rate of Incident Parkinson's Disease.

Background Although there is evidence of shared dysregulated pathways between diabetes and Parkinson's disease, epidemiologic research on an association between the two diseases has produced inconsistent results. Objective We aimed to assess whether known metabolomic markers of insulin resistance and diabetes are also associated with Parkinson's disease development. Methods We conducted a nested case-control study among Nurses' Health Study and Health Professionals Follow-up Study participants who had provided blood samples up to twenty years prior to Parkinson's diagnosis. Cases were matched to risk-set sampled controls by age, sex, fasting status, and time of blood collection. Participants provided covariate information via regularly collected cohort questionnaires. We used conditional logistic regression models to assess whether plasma levels of branched chain amino acids, acylcarnitines, glutamate, or glutamine were associated with incident development of Parkinson's disease. Results A total of 349 case-control pairs were included in this analysis. In the primary analyses, none of the metabolites of interest were associated with Parkinson's disease development. In investigations of the association between each metabolite and Parkinson's disease at different time intervals prior to diagnosis, some metabolites showed marginally significant association but, after correction for multiple testing, only C18 : 2 acylcarnitine was significantly associated with Parkinson's disease among subjects for whom blood was collected less than 60 months prior to case diagnosis. Conclusions Plasma levels of diabetes-related metabolites did not contribute to predict risk of Parkinson's disease. Further investigation of the relationship between pre-diagnostic levels of diabetes-related metabolites and Parkinson's disease in other populations is needed to confirm these findings.
Patrimoine linguistique au Kenya : Genèse et évolution du Sheng

La langue est un vecteur important de culture et donne expression au patrimoine d'un pays. Ca peut etre a la fois la forme et le contenu meme du patrimoine. D'ou la necessite de valoriser la langue comme patrimoine et expression de ce dernier. Le Kenya jouit d'une palette d'une quarantaine de langues africaines sans parler de l'anglais, la langue du pouvoir, et le swahili, la langue vehiculaire. Le sheng fait irruption au debut des annees 1950 comme langue hybride, combinant presque tous les idiomes en contact (swahili, anglais, langues vernaculaires, etc.). Etant donne que c'est la langue privilegiee des jeunes urbains et compte tenu de l'exode rural, il est important de considerer ce sous-langage et les dynamiques qui lui sont liees. Mots-cles : sheng, patrimoine, urbanisation, jeunesse.
Improving the safety of human pluripotent stem cell therapies using genome-edited orthogonal safeguards

Despite their rapidly-expanding therapeutic potential, human pluripotent stem cell (hPSC)-derived cell therapies continue to have serious safety risks. Transplantation of hPSC-derived cell populations into preclinical models has generated teratomas (tumors arising from undifferentiated hPSCs), unwanted tissues, and other types of adverse events. Mitigating these risks is important to increase the safety of such therapies. Here we use genome editing to engineer a general platform to improve the safety of future hPSC-derived cell transplantation therapies. Specifically, we develop hPSC lines bearing two drug-inducible safeguards, which have distinct functionalities and address separate safety concerns. In vitro administration of one small molecule depletes undifferentiated hPSCs >106-fold, thus preventing teratoma formation in vivo. Administration of a second small molecule kills all hPSC-derived cell-types, thus providing an option to eliminate the entire hPSC-derived cell product in vivo if adverse events arise. These orthogonal safety switches address major safety concerns with pluripotent cell-derived therapies.
The role of clonal haematopoiesis in cardiovascular diseases: epidemiology and experimental studies

Clonal haematopoiesis results from acquired mutations in haematopoietic stem and progenitor cells (HSPCs). These mutations can confer the HSPC with a competitive advantage, leading to their clonal expansion within the limiting bone marrow niche. This process is often insufficient to produce a haematologic malignancy; however, the expanding HSPC clones increasingly give rise to progeny leucocytes whose phenotypes can be altered by the somatic mutations that they harbour. Key findings from multiple human studies have shown that clonal haematopoiesis in the absence of overt haematologic alterations is common amongst the ageing population and associated with mortality and cardiovascular disease. Key findings from experimental studies have provided evidence for a causative role for clonal haematopoiesis in cardiovascular diseases, and aspects of these mechanisms have been elucidated. Whilst our understanding of the impact and biology of clonal haematopoiesis is in its infancy, analyses of some of the most commonly mutated driver genes suggest promising clinical scenarios involving the development of personalized therapies with immunomodulatory drugs that exploit the perturbation caused by the particular mutation. Herein, we review the accumulating epidemiological and experimental evidence, and summarize our current understanding of the importance of clonal haematopoiesis as a new causal risk factor for atherosclerotic cardiovascular disease and heart failure.