gebhart/patrepeval huggingface dataset:
Performance analysis of MAC-based beam tracking and failure detection and recovery (2021)

Several Medium Access Control (MAC) based beam management procedures have been adopted in the 3rd Generation Partnership Project (3GPP) to support beam-based communication in 5G New Radio (NR). These connected mode beam management functionalities include beam tracking, beam failure detection and beam failure recovery. This paper provides a detailed system-level performance analysis of beam management procedures for Frequency Range 1 (FR1) macro-cellular environments. Assumptions which are left open for User Equipment (UE) implementation are also discussed. Extensive system-level performance results for metrics such as beam failure probability, beam failure recovery, and beam time-of-stays are presented. We observe excellent beam management performance for UEs that are not about to experience handovers. On the other hand, UEs at the cell-edge are subject higher values, but still on an acceptable failure probability level of 1-2% for UE speeds up to 30 kmph.
Screening for noise in gene expression identifies drug synergies (2014)

Stochastic fluctuations are inherent to gene expression and can drive cell-fate specification. We used such fluctuations to modulate reactivation of HIV from latency-a quiescent state that is a major barrier to an HIV cure. By screening a diverse library of bioactive small molecules, we identified more than 80 compounds that modulated HIV gene-expression fluctuations (i.e., "noise"), without changing mean expression. These noise-modulating compounds would be neglected in conventional screens, and yet, they synergized with conventional transcriptional activators. Noise enhancers reactivated latent cells significantly better than existing best-in-class reactivation drug combinations (and with reduced off-target cytotoxicity), whereas noise suppressors stabilized latency. Noise-modulating chemicals may provide novel probes for the physiological consequences of noise and an unexplored axis for drug discovery, allowing enhanced control over diverse cell-fate decisions.
Role of membrane-associated folate binding protein in the cytotoxicity of antifolates in KB, IGROV1, and L1210A cells. (1995)

Based on differential levels of membrane-associated folate binding protein (mFBP) expression, murine L1210 leukemia, human KB epidermoid carcinoma, and human IGROV1 ovarian carcinoma cells maintained under low (physiological) folate conditions (2 nM folinic acid) were used as model systems to investigate the potential role of mFBP in antifolate transport. In addition, L1210 parental cells were compared to a subline, L1210A, expressing high levels of mFBP and defective reduced folate carrier. Antifolates for which KB-derived mFBP has high affinity (5, 10-dideazatetrahydrofolic acid [DDATHF] and homo-DDATHF [0.24 and 0.78 respectively relative to folic acid]) and low affinity (methotrexate [0.002]) were chosen for this study. Protection against DDATHF/homo-DDATHF induced cytotoxicity was achieved preferentially by folic acid compared to folinic acid in IGROV1 and L1210A cells. In IGROV1 cells, cytotoxicity IC50s were increased 18- and 5.5-fold for DDATHF and homo-DDATHF respectively by 20 nM folic acid. Moreover, greater protection was observed in L1210A cells, where IC50s were increased 354- and 80-fold for these same compounds by 20 nM folic acid. Similar protection was not observed in KB cells, suggesting that KB mFBP was not functional in DDATHF transport. Although mFBP expression may be an important determinant in the cytotoxicity of antifolates for certain tumor cells, our data demonstrate a lack of correlation between levels of mFBP and function of mFBP for DDATHF transport in the models studied.
European Sub-Registry of Chronic Myelogenous Leukemia (CML) Patients (pts) in Failure after Imatinib Therapy (IFP): Rationale, Study Design and Current Enrollment. (2006)

Abstract The purpose of the registry is to collect existing cases of pts who failed imatinib therapy. Since the drug has been registered most of information on safety and efficacy were collected through clinical trials. Thus the true rate of failure is currently unknown. Members of the European LeukemiaNet agreed to establish a subregistry with the aim of collecting these cases. Failure is defined as efficacy failure i.e. no hematological response (HR) or cytogenetic response (CyR), unsatisfactory response, loss of response, according to the European Guidelines criteria (Baccarani et al, Blood 2006) and documented toxicity leading to discontinuation of imatinib. Objectives are to describe the sub-categories of failure and main toxicities, demographic patterns, clinical and biological profiles of pts (at diagnosis, at the beginning of imatinib therapy, at time of failure), dose and duration of imatinib therapy until failure was recorded, therapeutic decision after failure, and survival status. Eligibility criteria: To be included in the Registry, pts who failed imatinib therapy must be 18 years old or more with Ph+ CML in chronic phase at the onset of imatinib therapy. Pts are eligible, being included in prospective studies or not. Data collection: based on notification, data is prospectively centralized and quality controlled. The planned period for registration is 2005–2007 and 1000 cases are expected. Final analyses will be conducted overall, by groups: imatinib first line/not first line and by categories of failures. Results: As of July, 2006, 378 pts,(M: 56%, F 44%), were recorded. Median age at diagnosis was 51 (range 12–80). Participating countries were: Austria (4 pts), Denmark (13), Finland (18), France (236), Germany (39), Israel (34), Italy (10), Netherlands (11), Spain (13). Thirty seven percent of pts were never included in prospective studies at the time of failure. Reason for registration was no or unsatisfactory response in 30% of the cases including no complete HR (2%), not any CyR (12%), no major CyR (16%). Loss of responses occurred in 41% of the cases including hematological relapse (6%) cytogenetic relapse or progression (12%), progression to accelerated phase or blast crisis (23%). Discontinuation because of toxicity was recorded in 13% of the cases. Sixteen percent of the pts presented toxicity combined with unsatisfactory response. Policy: The IFP sub-registry is supported by a grant from the 6th European framework program “LifeSciHealth”. This collaborative study is linked with the European CML Registry (Work Package 4). This study is conducted in accordance with principles and guidelines of the European Community and Helsinki protocol and was approved by French authorities. In conclusion, this registry has been successfully established and already provides important information on subcategories of imatinib failure pts.
Exchangeability of radioactive acetylcholine with the bound acetylcholine of synaptosomes and synaptic vesicles (1968)

1. The exchangeability with added radioactive acetylcholine of the acetylcholine in isolated presynaptic nerve terminals (synaptosomes) and isolated synaptic vesicles was studied by a Sephadex-column method. 2. A substantial proportion of the synaptosomal acetylcholine is exchangeable with added radioactive acetylcholine. It is liberated by hypo-osmotic shock and ultrasonic treatment, and behaves as though it occupies the cytoplasmic compartment of synaptosomes. 3. Methods of isolating vesicles from hypo-osmotically ruptured synaptosomes in optimum yield are discussed. 4. The acetylcholine of synaptic vesicles isolated on a sucrose density gradient is released by hypo-osmotic conditions, suggesting that it is enclosed by a semi-permeable membrane; however, it is not easily released by ultrasonic treatment. 5. Added radioactive acetylcholine does not exchange with vesicular acetylcholine under a variety of different conditions. These include addition of ATP and Mg(2+), and pre-loading of the synaptosome with radioactive acetylcholine before hypo-osmotic rupture. This failure to exchange is discussed in terms of the possible storage mechanism of vesicular acetylcholine.
CLN1 and Its Repression by Xbp1 Are Important for Efficient Sporulation in Budding Yeast (2000)

Xbp1, a transcriptional repressor of Saccharomyces cerevisiae with homology to Swi4 and Mbp1, is induced by stress and starvation during the mitotic cycle. It is also induced late in the meiotic cycle. Using RNA differential display, we find that genes encoding three cyclins (CLN1, CLN3, and CLB2), CYS3, and SMF2 are downregulated when Xbp1 is overexpressed and that Xbp1 can bind to sequences in their promoters. During meiosis, XBP1 is highly induced and its mRNA appears at the same time as DIT1 mRNA, but its expression remains high for up to 24 h. As such, it represents a new class of meiosis-specific genes. Xbp1-deficient cells are capable of forming viable gametes, although ascus formation is delayed by several hours. Furthermore, Xbp1 target genes are normally repressed late in meiosis, and loss of XBP1 results in their derepression. Interestingly, we find that a deletion of CLN1 also reduces the efficiency of sporulation and delays the meiotic program but that sporulation in a Deltacln1 Deltaxbp1 strain is not further delayed. Thus, CLN1 may be Xbp1's primary target in meiotic cells. We hypothesize that CLN1 plays a role early in the meiotic program but must be repressed, by Xbp1, at later stages to promote efficient sporulation.
The Stereochemistry of Complex Inorganic Compounds. XIII.1 A Partial Resolution of Racemic Tartaric Acid by Means of Different Stabilities of Isomers of Complex Ions2 (1952)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Stereochemistry of Complex Inorganic Compounds. XIII.1 A Partial Resolution of Racemic Tartaric Acid by Means of Different Stabilities of Isomers of Complex Ions2John C. Bailar Jr., Hans B. Jonassen, and Allan D. GottCite this: J. Am. Chem. Soc. 1952, 74, 12, 3131–3134Publication Date (Print):June 1, 1952Publication History Published online1 May 2002Published inissue 1 June 1952https://pubs.acs.org/doi/10.1021/ja01132a051https://doi.org/10.1021/ja01132a051research-articleACS PublicationsRequest reuse permissionsArticle Views110Altmetric-Citations13LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Synthesis and Properties of Isobicyclo‐DNA (2013)

We present the synthesis of the isobicyclo-DNA building blocks with the nucleobases A, C, G and T, as well as biophysical and biological properties of oligonucleotides derived thereof. The synthesis of the sugar part was achieved in 5 steps starting from a known intermediate of the tricyclo-DNA synthesis. Dodecamers containing single isobicyclo-thymidine incorporations, fully modified A- and T-containing sequences, and fully modified oligonucleotides containing all four bases were synthesized and characterized. Isobicyclo-DNA forms stable duplexes with natural nucleic acids with a pronounced preference for DNA over RNA as complements. The most stable duplexes, however, arise by self-pairing. Isobicyclo-DNA forms preferentially B-DNA-like duplexes with DNA and A-like duplexes with complementary RNA as determined by circular dichroism (CD) spectroscopy. Self-paired duplexes show a yet unknown structure, as judged from CD spectroscopy. Biochemical tests revealed that isobicyclo-DNA is stable in fetal bovine serum and does not elicit RNaseH activity.
Graft versus leukemia effect may overcome therapeutic resistance of chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy chain gene status (2004)

6525 Background: Although allogeneic SCT (allo-SCT) can result in long-term disease control in CLL, to date it is unknown to what extent graft-versus-leukemia activity (GVL) plays a role espescially in VH unmutated cases. We investigated whether the therapeutic resistance of unmutated CLL can be overcome by GVL in the context of allo-SCT following reduced-intensity conditioning (RIC) with fludarabine and cyclophosphamide. Methods: We prospectively measured the kinetics of residual disease (MRD) by real-time IgH PCR and donor chimerism in peripheral blood in 9 patients with unmutated CLL after RIC allo-SCT and compared to that of 29 unmutated patients who had undergone autologous SCT (auto-SCT). Results: After auto-SCT median MRD decreased immediately from 1.0E-2 pretransplant to 2.6E-4 at +3 months (p=0.0002) followed by a stable phase of about two years. Failure to achieve MRD negativity was associated with subsequent clinical relapse in 9 of 29 patients, with a median progression-free survival of 48 months post auto-SCT. Conditioning for allo SCT provided a moderate reduction of the median MRD level (5.4E-2 pretransplant vs. 5.0E-3 at +3 months). With reduction of immunosuppression, however, MRD levels progressively declined to 8.5E-5 at +6 months (p=0.005) and to MRD negativity at +12 months in 7 of 9 patients. With a median follow-up of 21 (11–35) months, these 7 patients remain in continuing clinical and molecular remission, althoug one patient shows still mixed chimerism. One patient died from progressive nodular disease with MRD levels at 1E-4, another patient with slowly increasing MRD-level presents still subclinical CLL. Conclusion: A progressive decline of MRD levels to negativity can be obtained after RIC allo-SCT but not after auto-SCT for unmutated CLL, suggesting a crucial role of GVL-mediated immunotherapy for complete disease eradication in this high-risk subset. No significant financial relationships to disclose.
Direct targeting of wild-type glucocerebrosidase by antipsychotic quetiapine improves pathogenic phenotypes in Parkinson’s disease models (2021)

Current treatments for Parkinson's disease (PD) provide only symptomatic relief, with no disease-modifying therapies identified to date. Repurposing FDA-approved drugs to treat PD could significantly shorten the time needed for and reduce the costs of drug development compared with conventional approaches. We developed an efficient strategy to screen for modulators of β-glucocerebrosidase (GCase), a lysosomal enzyme that exhibits decreased activity in patients with PD, leading to accumulation of the substrate glucosylceramide and oxidized dopamine and α-synuclein, which contribute to PD pathogenesis. Using a GCase fluorescent probe and affinity-based fluorescence polarization assay, we screened 1280 structurally diverse, bioactive, and cell-permeable FDA-approved drugs and found that the antipsychotic quetiapine bound GCase with high affinity. Moreover, quetiapine treatment of induced pluripotent stem cell-derived (iPSC-derived) dopaminergic neurons from patients carrying mutations in GBA1 or LRRK2 led to increased wild-type GCase protein levels and activity and partially lowered accumulation of oxidized dopamine, glucosylceramide, and α-synuclein. Similarly, quetiapine led to activation of wild-type GCase and reduction of α-synuclein in a GBA mutant mouse model (Gba1D409V/+ mice). Together, these results suggest that repurposing quetiapine as a modulator of GCase may be beneficial for patients with PD exhibiting decreased GCase activity.
Lane change path planning based on piecewise Bezier curve for autonomous vehicle (2013)

Autonomous vehicle is an efficient component in vehicle active system to reduce traffic accidents. The path planning of lane change for autonomous vehicle is an important component in the autonomous vehicle field. In order to generate a path for passing the front vehicle, a new path planning method that is curvature-continuous and satisfies the vehicle nonholonomic constraint is introduced. Firstly, we calculate the safe lane change distance for autonomous vehicle. Secondly, we generate the path based on piecewise quadratic Bezier curve and the maximum curvature of the Bezier curves is calculated to verify whether the autonomous vehicle can follow this path. Then, we present the indicator based on yaw-rate of vehicle to verify the vehicle ride comfort. The experiment results show that the path generated by this method can be successfully executed by autonomous vehicle, the curvature of the path is continuous, meanwhile vehicle nonholonomic and ride comfort indicator constraint condition is met.
Deep-Depletion diamond metal-oxide-semiconductor field-effect transistor with source-field plate for power converters (2022)

International audience
Cellular energetics in hypothyroid muscle (1992)

Skeletal muscle of seven hypothyroid patients was investigated in the resting state and during exercise and recovery using 31P magnetic resonance spectroscopy. The bioenergetics and intracellular pH of the hypothyroid muscle were thus evaluated and compared with results from normal muscle and muscle of patients with mitochondrial myopathy. In resting hypothyroid muscle there were significant elevations in the concentration ratios of phosphocreatine/ATP and inorganic phosphate/ATP, while phosphocreatine/inorganic phosphate and intracellular pH were lower than normal. In exercising hypothyroid muscle, energy stores were depleted more rapidly and acidification began later than in normal muscle. Recovery of phosphocreatine to the pre-exercise value was normal, but intracellular pH recovered slowly. The data suggest that in the hypothyroid state, glycogen breakdown in skeletal muscle was delayed thereby limiting the substrate supply for both glycolytic and oxidative production of ATP at the beginning of exercise. There was no evidence for a decrease in the oxidative capacity of the muscle of our patients, but elevated ADP may have stimulated oxidative metabolism and helped to compensate for low mitochondrial content. The low intracellular pH in resting muscle and the slow pH recovery after exercise imply that proton handling was abnormal in the hypothyroid muscle.
Swarming Geographic Event Profiling, Link Analysis, and Prediction (2009)

Geographically embedded processes with hidden origins are often observable in events they generate. It is common practice in criminological forensics to reverse simple equation-based models of trajectories that link the origin with its events to derive a probability estimate of a common origin location. This approach requires that linked events are manually extracted from larger event data sets. Also, as this approach is equation-based, it is generally not possible to take into account any specific geographic characteristics that may affect the trajectory. In this paper, we present a swarming model of simple geographic agents who reason "backward" from large sets of events to origin location probability distributions, use the overlap of these distributions to identify clusters of events that may share a common origin, and then reason "forward" from the clusters' origin distributions to predict the risk of future events. We apply this model to the domain of Improvised Explosive Devices (IEDs).
Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration (2012)

The BM microenvironment is required for the maintenance, proliferation, and mobilization of hematopoietic stem and progenitor cells (HSPCs), both during steady-state conditions and hematopoietic recovery after myeloablation. The ECM meshwork has long been recognized as a major anatomical component of the BM microenvironment; however, the molecular signatures and functions of the ECM to support HSPCs are poorly understood. Of the many ECM proteins, the expression of tenascin-C (TN-C) was found to be dramatically up-regulated during hematopoietic recovery after myeloablation. The TN-C gene was predominantly expressed in stromal cells and endothelial cells, known as BM niche cells, supporting the function of HSPCs. Mice lacking TN-C (TN-C(-/-)) mice showed normal steady-state hematopoiesis; however, they failed to reconstitute hematopoiesis after BM ablation and showed high lethality. The capacity to support transplanted wild-type hematopoietic cells to regenerate hematopoiesis was reduced in TN-C(-/-) recipient mice. In vitro culture on a TN-C substratum promoted the proliferation of HSPCs in an integrin α9-dependent manner and up-regulated the expression of the cyclins (cyclinD1 and cyclinE1) and down-regulated the expression of the cyclin-dependent kinase inhibitors (p57(Kip2), p21(Cip1), p16(Ink4a)). These results identify TN-C as a critical component of the BM microenvironment that is required for hematopoietic regeneration.
A STUDY OF MULTISTAGE INTERCONNECTION NETWORKS: DESIGN, DISTRIBUTED CONTROL, FAULT TOLERANCE, AND PERFORMANCE (ADM, IADM) (1982)

The interconnection of a large number of processors and other devices to form a large-scale parallel/distributed computing system is a research area receiving a great deal of attention. To characterize the operating environment of such systems, seven different proposed and/or built, large-scale computers are examined and described. A major consideration in the development of these parallel processing systems is the design of the interconnection network that is to provide communications among the processors and other devices. To gain proper historical perspective, 17 networks and seven classes of networks are surveyed, beginning with the early telephone switching networks. A family tree showing their relationship to each other is included. From the survey, two major classes are identified: the cube type and the data manipulator type. In the research presented, the Generalized Cube network is used to represent the former and the augmented data manipulator (ADM) and inverse ADM (IADM) networks are used to represent the latter. These three networks are examined and compared. The architecture of the switching elements for the networks is studied in depth. Different designs are compared in terms of cost and performance. Using a graph theoretic approach, Generalized Cube and ADM networks of comparable size are evaluated in terms of total cost and inherent fault tolerance or robustness. For large scale systems, it is important to distribute control of the network among its users (e.g. processors), to avoid the bottleneck that could occur in a centralized controller. Routing tag schemes are developd for the networks for this purpose. Both one-to-one and one-to-many or broadcast communications are supported. Since the ADM and IADM networks are known to have multiple source to destination paths, methods for dynamically switching between paths using routing tags are investigated to avoid busy or faulty links and switching elements. Finally, fault tolerance is considered. Methods to exploit the inherent fault tolerance of the IADM network by adding some extra hardware are explored. The affect of additional hardware on the routing tag scheme is taken into account.