julilili42/papers huggingface dataset:
Simulating the response of a neuro-musculoskeletal model to assistive forces: implications for the design of wearables compensating for motor control deficits
2020-10-15

Models of the human arm may help to estimate design parameters like peak torque and power of wearable assistive devices by predicting required forces to compensate for motor control impairments. This work focuses on the idea of compensating hypermetria (overshoot)-a motor control deficit that may occur in neurodegenerative diseases-by a simple assistive device. As musculoskeletal dynamics play an important role in the interaction between an assistive device and the neuro-musculoskeletal system, we hypothesized that their consideration in the model might influence the predicted design parameters. To test this, we simulated two-degree-of-freedom point-to-point arm movements. By introducing inconsistent neuronal control parameters, we induced hypermetria. We implemented mechanical and low-level assistive torque strategies in simulation which lead to a reduction of hypermetria. We found that-depending on the type of assistance-the predicted torques and powers can differ by more than a factor of 10 between musculoskeletal and torque-driven arm models. We conclude that the magnitude of torque and power required to reduce hypermetria by simple wearable assistive devices may be significantly underestimated if muscle-tendon characteristics are not considered.
Relapse After Early-Stage, Favorable Hodgkin Lymphoma: Disease Characteristics and Outcomes With Conventional or High-Dose Chemotherapy
2020-10-15

PURPOSE We evaluated disease and treatment characteristics of patients with relapse after risk-adapted first-line treatment of early-stage, favorable, classic Hodgkin lymphoma (ES-HL). We compared second-line therapy with high-dose chemotherapy and autologous stem cell transplantation (ASCT) or conventional chemotherapy (CTx). METHODS We analyzed patients with relapse after ES-HL treated within the German Hodgkin Study Group HD10+HD13 trials. We compared, by Cox proportional hazards regression, progression-free survival (PFS) after relapse (second PFS) treated with either ASCT or CTx and performed sensitivity analyses with overall survival (OS) from relapse and Kaplan-Meier statistics. RESULTS A total of 174 patients’ disease relapsed after treatment in the HD10 (n = 53) and HD13 (n = 121) trials. Relapse mostly occurred &gt; 12 months after first diagnosis, predominantly with stage I-II disease. Of 172 patients with known second-line therapy, 85 received CTx (49%); 70, ASCT (41%); 11, radiotherapy only (6%); and 4, palliative single agent therapies (2%). CTx was predominantly bleomycin, etoposide, doxorubicin cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP [68%]), followed by the combination regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (19%), or other regimens (13%). Patients aged &gt; 60 years at relapse had shorter second PFS (hazard ratio [HR], 3.0; P = .0029) and were mostly treated with CTx (n = 33 of 49; 67%) and rarely with ASCT (n = 8; 16%). After adjustment for age and a disadvantage of ASCT after the more historic HD10 trial, we did not observe a significant difference in the efficacy of CTx versus ASCT for second PFS (HR, 0.7; 95% CI, 0.3 to 1.6; P = .39). In patients in the HD13 trial who were aged ≤ 60 years, the 2-year, second PFS rate was 94.0% with CTx (95% CI, 85.7% to 100%) versus 83.3% with ASCT (95% CI, 71.8% to 94.8%). Additional sensitivity analyses including OS confirmed these observations. CONCLUSION After contemporary treatment of ES-HL, relapse mostly occurred &gt; 12 months after first diagnosis. Polychemotherapy regimens such as BEACOPP are frequently administered and may constitute a reasonable treatment option for selected patients with relapse after ES-HL.
Assessing and Overcoming Resistance Phenomena against a Genetically Modified Vaccinia Virus in Selected Cancer Cell Lines
2020-10-15

Genetically modified vaccinia viruses (VACVs) have been shown to possess profound oncolytic capabilities. However, tumor cell resistance to VACVs may endanger broad clinical success. Using cell mass assays, viral replication studies, and fluorescence microscopy, we investigated primary resistance phenomena of cell lines of the NCI-60 tumor cell panel to GLV-1h94, a derivative of the Lister strain of VACV, which encodes the enzyme super cytosine deaminase (SCD) that converts the prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic compound 5-fluorouracil (5-FU). After treatment with GLV-1h94 alone, only half of the cell lines were defined as highly susceptible to GLV-1h94-induced oncolysis. When adding 5-FC, 85% of the cell lines became highly susceptible to combinatorial treatment; none of the tested tumor cell lines exhibited a “high-grade resistance” pattern. Detailed investigation of the SCD prodrug system suggested that the cytotoxic effect of converted 5-FU is directed either against the cells or against the virus particles, depending on the balance between cell line-specific susceptibility to GLV-1h94-induced oncolysis and 5-FU sensitivity. The data provided by this work underline that cellular resistance against VACV-based virotherapy can be overcome by virus-encoded prodrug systems. Phase I/II clinical trials are recommended to further elucidate the enormous potential of this combination therapy.
SynBio‐SynChem Approaches to Diversifying the Pacidamycins through the Exploitation of an Observed Pictet‐Spengler Reaction
2020-10-15

Abstract A nonenzymatic Pictet‐Spengler reaction has been postulated to give rise to a subset of naturally occurring uridyl peptide antibiotics (UPAs). Here, using a combination of strain engineering and synthetic chemistry, we demonstrate that Pictet‐Spengler chemistry may be employed to generate even greater diversity in the UPAs. We use an engineered strain to afford access to meta‐ tyrosine containing pacidamycin 4. Pictet‐Spengler diversification of this compound using a small series of aryl‐aldehydes was achieved with some derivatives affording remarkable diastereomeric control.
Teaching primary school children about computer viruses
2020-10-15

Children increasingly use computing devices. However, it is unclear whether they have basic knowledge of security-related issues such as computer viruses and, in case they do not, what they can learn about them. In this study, we first examined preconceptions of computer viruses among Czech and German primary school students using a newly developed test. Second, the experimental group (but not the control group) received an intervention to learn about computer viruses, antiviruses, and software updates by means of a 45-min lesson combining a cartoon series on viruses, frontal instruction, and discussion. Both groups again completed the test. A preliminary analysis indicated that Czech and German children already knew key points concerning computer viruses. However, overall, their knowledge was patchy, and children also had various misconceptions. The experimental group improved from pre- to posttest (d = 1.06), while this was not the case for the control group. These initial results indicated that knowledge of computer viruses should and can be taught to primary school children.
Baton Rouge (Louisiana): On the Importance of Thematic Cartography for 'Neopragmatic Horizontal Geography’
2020-10-16

Abstract The presented contribution is based on the testing of a 'neopragmatic' access to spaces in the context of horizontal geography using the case study of Baton Rouge, Louisiana (USA). In this approach, the focus is less on the theoretical framing or the detailed development of community development, but rather on the importance of thematic cartography in the neopragmatic approach of regional geography. The neopragmatic approach prioritizes the multi-perspective study of spatial constellations over theoretical 'purity' and methodological clarity. The investigation is 'horizontally' oriented and is characterized by the constructivist framed synthesis of research results from different disciplines (e.g., on economic or structural development).
Interaction signatures and non-Gaussian photon states from a strongly driven atomic ensemble coupled to a nanophotonic waveguide
2020-10-16

We study theoretically a laser-driven one-dimensional chain of atoms interfaced with the guided optical modes of a nanophotonic waveguide. The period of the chain and the orientation of the laser field can be chosen such that emission occurs predominantly into a single guided mode. We find that the fluorescence excitation line shape changes as the number of atoms is increased, eventually undergoing a splitting that provides evidence for the waveguide-mediated all-to-all interactions. Remarkably, in the regime of strong driving the light emitted into the waveguide is non-classical, with a significant negativity of the associated Wigner function. We show that both the emission properties and the non-Gaussian character of the light are robust against voids in the atom chain, enabling the experimental study of these effects with present-day technology. Our results offer a route towards novel types of fiber-coupled quantum light sources and an interesting perspective for probing the physics of interacting atomic ensembles through light.
Experiences With Health Care Services in Switzerland Among Immigrant Women With Chronic Illnesses
2020-10-16

<b>Introduction:</b> Descriptive data indicate a high burden of chronic illness among immigrant women in Switzerland. Little is known about how immigrant women with chronic illnesses experience healthcare services. This paper presents a methodological approach theoretically informed by Sen's capability approach and Levesque's framework of access to healthcare to study patient-reported experiences (PREs) of Swiss healthcare services among immigrant women with chronic conditions. <b>Methods:</b> We conducted 48 semi-structured qualitative interviews in Bern and Geneva with Turkish (<i>n</i> = 12), Portuguese (<i>n</i> = 12), German (<i>n</i> = 12), and Swiss (<i>n</i> = 12) women. Participants were heterogenous in age, length of stay, SES, and educational attainment, illness types and history. We also conducted semi-structured interviews with healthcare and social service providers (<i>n</i> = 12). Interviewed women participated in two focus group discussions (<i>n</i> = 15). Interviews were transcribed verbatim and analyzed using Atlas.ti software, based on Gale et al.'s framework approach. Findings informed three stakeholder dialogues in which women as well as healthcare providers and policymakers from various territorial levels participated. <b>Results:</b> Our methodological approach succeeded in integrating women's perspectives-from initial data collection in interviews to identify issues, focus group discussions to increase rigor, and stakeholder dialogues to develop tailored recommendations based on PREs. <b>Discussion:</b> This is one of the first studies in Switzerland that used PREs to research healthcare services and healthcare needs among immigrant women with chronic illnesses. This paper provides new insights on how to better understand existing challenges and potentially improve access to and quality of care.
Are Compounds Membrane-Associated or Present in the Cytosol? A Study Using Polyphenols in a Colon Carcinoma Cell Line Model
2020-10-16

Abstract Purpose We investigated the cytosolic and membrane-associated contents of polyphenols after 4 hours of incubation (50 μM of each polyphenol) in the colon carcinoma cell line T84 using a novel, rapid, and convenient method based on permeabilization of the cell membrane using digitonin. The colon carcinoma cell line was used to investigate the intestinal uptake of polyphenols present in apple products. Recent Findings The results showed that hydroxycinnamic acids (caffeic and 5-caffeoylquinic acid) were only detected in the cytosolic fractions. In contrast, 0.3 to 8.2% of the initial concentrations (50 μM) of the flavonoids phloretin, quercetin, phloretin 2′- O -glucoside, and quercetin 3- O -rhamnoside were found in the membrane-associated fractions. In the cytosolic fractions, 0.2–2.9% of these compounds were detected, corresponding to 25 to 40% of the total cell-associated (cytosolic plus membrane-associated fractions) polyphenol content. Summary Our results showed that after uptake, polyphenols were present in the cytosolic fraction of the cells as well as associated with the cell membrane. The presented method provides a useful in vitro tool for determining biologically active compounds in cellular fractions.
Cerebral Autoregulation and Neurovascular Coupling after Craniospinal Irradiation in Long-Term Survivors of Malignant Pediatric Brain Tumors of the Posterior Fossa
2020-10-16

Abstract Introduction Long-term survivors of craniospinal irradiation have an increased risk for stroke which increases with radiation dose and follow-up time. Radiotherapy induces structural changes of the cerebral vasculature, affecting both, large, and small vessels. It is unknown how these structural changes affect functional mechanisms of cerebral blood flow regulation such as cerebral autoregulation and neurovascular coupling. Methods Using the transcranial Doppler, we compared dynamic cerebral autoregulation and neurovascular coupling of 12 patients after long-term survival of craniospinal irradiation due to a malignant pediatric brain tumor of the posterior fossa and 12 age- and sex-matched healthy patients. Mean arterial blood pressure and cerebral blood flow velocities in the middle and posterior cerebral artery were recorded at rest during normal breathing to assess cerebral autoregulation (transfer function parameters phase and gain, as well as the correlation coefficient indices Mx, Sx, and Dx), and during 10 cycles of a visual task to assess neurovascular coupling (parameters time delay, natural frequency, gain, attenuation, and rate time). Results Parameters of cerebral autoregulation showed a consistent trend toward reduced cerebral autoregulation in patients that did not reach statistical significance. Neurovascular coupling was not altered after craniospinal irradiation. Conclusion In this pilot study, we demonstrated a trend toward reduced cerebral autoregulation, and no alteration of neurovascular coupling after irradiation in long-term survivors of malignant pediatric brain tumors of the posterior fossa.
On the Possibility of Dibaryon Formation near the N*(1440)N threshold
2020-10-16

The excitation of the Roper resonance in collisions leading to single and double pion production exhibits a structure in the energy dependence of the total cross section, which does not correspond to the usual opening of the production channel, but rather to the formation of dibaryon states with and at the threshold. This is very similar to the situation at the threshold, where meanwhile a number of dibaryonic resonances have been found.
NAMPT/SIRT2–mediated inhibition of the p53-p21 signaling pathway is indispensable for maintenance and hematopoietic differentiation of human iPS cells
2020-10-16

<title>Abstract</title> <bold>Background:</bold> Nicotinamide phosphoribosyltransferase (NAMPT) regulates cellular functions through the protein deacetylation activity of nicotinamide adenine dinucleotide (NAD<sup>+</sup>)-dependent sirtuins (SIRTs). SIRTs regulate functions of histones and none-histone proteins. The role of NAMPT/SIRTs pathway in the regulation of maintenance and differentiation of human induced pluripotent stem (iPS) cells is not fully elucidated.<bold>Methods:</bold> We evaluated the effects of specific inhibitors of NAMPT-, or SIRT2 on the pluripotency, proliferation, survival and hematopoietic differentiation of human iPS cells. We also studied the molecular mechanism downstream of NAMPT/SIRTs in iPS cells.<bold>Results:</bold> We demonstrated that NAMPT is indispensable for the maintenance, survival and hematopoietic differentiation of induced pluripotent stem (iPS) cells. We found that inhibition of NAMPT or SIRT2 in iPS cells induces p53 protein by promoting its lysine acetylation. This leads to activation of the p53 target, p21, with subsequent cell cycle arrest and induction of apoptosis in iPS cells. NAMPT and SIRT2 inhibition also affect hematopoietic differentiation of iPS cells in an embryoid body (EB)-based cell culture system.<bold>Conclusions:</bold> Our data demonstrate the essential role of the NAMPT/SIRT2/p53/p21 signaling axis in the maintenance and hematopoietic differentiation of iPS cells.
Using eye-tracking and EEG to study the mental processing demands during learning of text-picture combinations
2020-10-17

Using and combining eye-tracking and EEG frequency band power as process measures, in the current study we were interested in the mental processing demands during learning of text-picture combinations that either enabled or prohibited text-picture integration (TPI). In the mismatch condition, the textual and pictorial information being dissimilar, TPI was not possible, whereas in the match and the partial-match condition, the textual and pictorial information being identical respective complementary, TPI was possible. We expected mental processing demands to be higher in the mismatch condition, when pictorial and textual information had to be processed and memorized as separate representations, compared to the match and partial-match conditions when TPI was possible. As expected, on virtually all process measures we observed increased mental processing demands when two mental representations had to be processed and memorized compared to the two conditions where TPI was possible. The EEG alpha and theta frequency band power data corroborated and extended the eye-tracking measures of mental processing demands. In addition, we performed a fixation-related EEG frequency band power analysis that also corroborated the results of the classic stimulus-locked EEG frequency band power analysis, exemplifying the use of this former methodology in the context of complex multimedia task materials.
Seismic Anisotropy of Temperate Ice in Polar Ice Sheets
2020-10-17

Abstract We present a series of simple shear numerical simulations of dynamic recrystallization of two‐phase nonlinear viscous materials that represent temperate ice. First, we investigate the effect of the presence of water on the resulting microstructures and, second, how water influences on P wave ( V p ) and fast S wave ( V s ) velocities. Regardless the water percentage, all simulations evolve from a random fabric to a vertical single maximum. For a purely solid aggregate, the highest V p quickly aligns with the maximum c ‐axis orientation. At the same time, the maximum c ‐axis development reduces V s in this orientation. When water is present, the developed maximum c ‐axis orientation is less intense, which results in lower V p and V s . At high percentage of water, V p does not align with the maximum c ‐axis orientation. If the bulk modulus of ice is assumed for the water phase (i.e., implying that water is at high pressure), we find a remarkable decrease of V s while V p remains close to the value for purely solid ice. These results suggest that the decrease in V s observed at the base of the ice sheets could be explained by the presence of water at elevated pressure, which would reside in isolated pockets at grain triple junctions. Under these conditions water would not favor sliding between ice grains. However, if we consider that deformation dominates over recrystallization, water pockets get continuously stretched, allowing water films to be located at grain boundaries. This configuration would modify and even overprint the maximum c ‐axis‐dependent orientation and the magnitude of seismic anisotropy.
Auditory and Somatosensory P3 Are Complementary for the Assessment of Patients with Disorders of Consciousness
2020-10-17

The evaluation of the level of consciousness in patients with disorders of consciousness (DOC) is primarily based on behavioural assessments. Patients with unresponsive wakefulness syndrome (UWS) do not show any sign of awareness of their environment, while minimally conscious state (MCS) patients show reproducible but fluctuating signs of awareness. Some patients, although with remaining cognitive abilities, are not able to exhibit overt voluntary responses at the bedside and may be misdiagnosed as UWS. Several studies investigated functional neuroimaging and neurophysiology as an additional tool to evaluate the level of consciousness and to detect covert command following in DOC. Most of these studies are based on auditory stimulation, neglecting patients suffering from decreased or absent hearing abilities. In the present study, we aim to assess the response to a P3-based paradigm in 40 patients with DOC and 12 healthy participants using auditory (AEP) and vibrotactile (VTP) stimulation. To this end, an EEG-based brain-computer interface was used at DOC patient’s bedside. We compared the significance of the P3 performance (i.e., the interpretation of significance of the evoked P3 response) as obtained by ‘direct processing’ (i.e., theoretical-based significance threshold) and ‘offline processing’ (i.e., permutation-based single subject level threshold). We evaluated whether the P3 performances were dependent on clinical variables such as diagnosis (UWS and MCS), aetiology and time since injury. Last we tested the dependency of AEP and VTP performances at the single subject level. Direct processing tends to overestimate P3 performance. We did not find any difference in the presence of a P3 performance according to the level of consciousness (UWS vs. MCS) or the aetiology (traumatic vs. non-traumatic brain injury). The performance achieved at the AEP paradigm was independent from what was achieved at the VTP paradigm, indicating that some patients performed better on the AEP task while others performed better on the VTP task. Our results support the importance of using multimodal approaches in the assessment of DOC patients in order to optimise the evaluation of patient’s abilities.
ER-to-Golgi Transport in HeLa Cells Displays High Resilience to Ca2+ and Energy Stresses
2020-10-17

One third of all human proteins are either transmembrane or soluble secretory proteins that first target the endoplasmic reticulum (ER). These proteins subsequently leave the ER and enter the Golgi apparatus via ER-Golgi intermediate vesicular structures. Live-cell imaging of cargos fused to fluorescent proteins (FPs) enables the high-resolution visualization and characterization of secretory transport processes. Here, we performed fluorescence time-lapse imaging to assess the Ca2+ and energy dependency of ER-to-Golgi transport in living HeLa cells, a cancer cell model which has been well investigated. Our data revealed that ER-to-Golgi transport remained highly efficient in the absence of ATP-generating substrates, despite clear reductions in cytosolic and mitochondrial ATP levels under these energy stress conditions. However, cell treatment with 2-deoxy-D-glucose (2-DG), which severely diminished subcellular ATP levels, abolished ER-to-Golgi transport. Interestingly, while 2-DG elevated cytosolic Ca2+ levels and reduced long-distance movements of glycosylphosphatidylinositol (GPI)-positive vesicles, robust short-term ER Ca2+ mobilizations, which strongly affected the motility of these vesicles, did not considerably impair ER-to-Golgi transport. In summary, we highlight that ER-to-Golgi transport in HeLa cells remains functional despite high energy and Ca2+ stress levels.