gebhart/patrepeval huggingface dataset:
An Autosomal Dominant SCID Form Due to a Gain of Function Mutation in the RAC2 Gene (2019)

Severe combined immunodeficiencies (SCIDs) form a heterogeneous group of life-threatening genetic disorders defined by the absence of autologous T cells and an intrinsic or extrinsic defect in the B-cell compartment. In our cohort, three newborn patients with bone-marrow hypoplasia associated with clinical and biological features of SCID received allogenic hematopoietic stem cell transplantation in the first weeks of life. To identify the molecular defect involved in this life threatening SCID form, we performed whole-genome sequencing on patient's fibroblasts. The same heterozygous, dominant missense mutation was found in the RAC2gene encoding for the RAC2 GTPase (p.G12R). By biochemical analyses we demonstrated that arginine substitution at position 12 leads to sustained activation of the RAC2 signalling pathway; the G12R mutation is therefore a gain of function mutation. In cord blood hematopoietic cells, we observed that the mutation disrupts mitochondrial activity and blocks hematopoietic stem/progenitor cells (HSPCs) differentiation toward the myeloid and lymphoid lineages. Altogether, our data emphasize the involvement of the RAC2 signalling pathway during hematopoeisis and might thus explain the severity of the patients' clinical and immunological phenotype. The present study is the first to report an autosomal dominant form of SCID and suggest that RAC2 gene sequencing should be considered for patients with SCID clinical presentation. Disclosures Cavazzana: Smartimmune: Other: Founder of Smartimmune.
Amino acid sensing in hypothalamic tanycytes via umami taste receptors (2017)

Two receptors previously implicated in taste cells, the Tas1r1/Tas1r3 heterodimer and mGluR4, contribute to the detection of a range of amino acids by tanycytes in CSF.
Infection of Mice Lacking Interleukin-7 (IL-7) Reveals an Unexpected Role for IL-7 in the Development of the ParasiteSchistosoma mansoni (1999)

A single intradermal administration of recombinant interleukin-7 (IL-7) has been shown to aggravate the course of murine schistosomiasis, to favor the development of Th2-associated antibodies specific for the parasite, and to alter migration kinetics and/or migratory route of the parasite within its vertebrate host. Here we show that after infection of IL-7-deficient mice with Schistosoma mansoni, the predominant parasite-specific humoral response follows a Th1 pattern, and the development of the parasite is greatly impaired. In IL-7-deficient mice, increased numbers of larvae reach the lungs and fewer larvae reach the liver, compared to control mice. In the absence of IL-7, female worms show an altered fecundity, leading to decreased numbers of eggs trapped in the tissues and to an amelioration of the pathology of the infected host. The most striking observation is the blockade of parasite growth in an IL-7-defective environment, leading to dwarf male and female worms. The results of this study have important implications for the role of IL-7 in the host-parasite relationship and show how parasites can disable or evade the host immune response.
Comparison of laser desorption and matrix-assisted laser desorption/ionization for ruthenium and osmium trisbipyridine complexes using Fourier transform mass spectrometry (2003)

Metal-bipyridine complexes are a vehicle for developing approaches for studying the fluorescence of gas-phase ions; however, conclusions regarding fluorescence behavior depend on explicitly identifying the ionic species in the gas phase. [Ru(bpy)(3)]X(2) and [Os(bpy(3))]X(2), (where bpy = 2,2'-bipyridine and X = Cl or PF(6)), were studied using direct laser desorption (LD) and matrix-assisted laser desorption/ionization (MALDI) using Fourier transform mass spectrometry (FTMS). LD spectra of the PF(6) salt of the Ru and Os complexes reveal counterion attachment, fluoride transfer, and significant losses of H for a number of peaks. LD of the chloride salt complexes produced loss of a single bpy ligand, chloride attachment, and losses of H. Spectra of [Ru(bpy(3)]X(2) where X = BF(4)(-), CF(3)SO(3)(-), and SCN(-) were also collected using LD and compared with the spectra for Cl(2) and PF(6) salts. Regardless of counterion, loss of H is observed in LD spectra. MALDI spectra of the trisbipyridyl complexes using 2,5-dihydroxybenzoic acid (DHB) and sinapinic acid (SA) as the matrix were also obtained. The spectra using SA as matrix show intact molecular ion peaks with very little fragmentation and no counterion attachment. Unlike SA, the spectra obtained using DHB look similar to LD spectra with significant losses of H. Our results are consistent with a reaction scheme for hydrogen loss from a carbon that also involves breaking of the metalz.sbnd;nitrogen bond, rotation of a pyridine ring, and re-formation of an ortho-metallated complex by a metalz.sbnd;C bond. These results demonstrate the importance of ion generation method and the utilization of FTMS for correct characterization of metal poly(pyridyl) complexes.
Development of 4-D High-Resolution CT for Measurement of Airway Deformation (2007)

Airway consists of a number of various compliant tubes from trachea to alveolus, and the airway geometry deforms dramatically during respiration. This morphometric deformation is very important factors in pulmonary dynamics (flow structure, particle deposition, surfactant transport and so on). Previously, we reported the small airway deformations of euthanized animals using micro-CT and synchrotron radiation-CT.
Monolithic Silicon Coherent Receiver (2009)

We realized a monolithic polarization-diversity dual-quadrature coherent receiver with on-chip balanced detection in a silicon photonic integrated circuit with integrated germanium detectors. We tested it using a polarization-division multiplexed quadrature phase-shift keyed signal at 112-Gb/s.
Vibrational resonant desorption from surfaces using the infrared free-elctron laser (1990)

The IRFEL is a useful infrared light source that can be employed as a probe of vibrational dynamics on surfaces. This paper will discuss the application of the IRFEL to desorb adsorbates from surfaces by resonantly exciting their vibrational modes. This application is illustrated by recent investigations of the resonant desorption of butane from Al2O(1120) using the Mark III IRFEL. These resonant desorption studies revealed a greater desorption yield for the asymmetric C-H stretches in comparison with the symmetric C-H stretches. This greeter desorption efficiency for the asymmetric C-H stretches was attributed to the orientation of the butane molecules in an ordered adlayer on A1203 (1120).
Distributed Stochastic Gradient Descent and Convergence to Local Minima (2020)

In centralized settings, it is well known that stochastic gradient descent (SGD) avoids saddle points. However, similar guarantees are lacking for distributed first-order algorithms in nonconvex optimization.The paper studies distributed stochastic gradient descent (D-SGD)--a simple network-based implementation of SGD. Conditions under which D-SGD converges to local minima are studied. In particular, it is shown that, for each fixed initialization, with probability 1 we have that: (i) D-SGD converges to critical points of the objective and (ii) D-SGD avoids nondegenerate saddle points. To prove these results, we use ODE-based stochastic approximation techniques. The algorithm is approximated using a continuous-time ODE which is easier to study than the (discrete-time) algorithm. Results are first derived for the continuous-time process and then extended to the discrete-time algorithm. Consequently, the paper studies continuous-time distributed gradient descent (DGD) alongside D-SGD. Because the continuous-time process is easier to study, this approach allows for simplified proof techniques and builds important intuition that is obfuscated when studying the discrete-time process alone.
Bipolar disorder type I and II show distinct relationships between cortical thickness and executive function (2018)

Our findings suggest that bipolar disorder patients show altered structure-function relationships, and importantly that those relationships may differ between bipolar subtypes. The findings are line with studies suggesting subtype-specific neurobiological and cognitive profiles. This study contributes to a better understanding of brain structure-function relationships in bipolar disorder and gives important insights into the neuropathophysiology of diagnostic subtypes.
Molecular Imaging Reveals Skeletal Engraftment Sites of Transplanted Bone Marrow Cells (2006)

Molecular imaging holds great promise for the in vivo study of cell therapy. Our hypothesis was that multimodality molecular imaging can identify the initial skeletal engraftment sites post-bone marrow cell transplantation. Utilizing a standard mouse model of bone marrow (BM) transplantation, we introduced a combined bioluminescence (BLI) and positron emission tomography (PET) imaging reporter gene into mouse bone marrow cells. Bioluminescence imaging was used for monitoring serially the early in vivo BM cell engraftment/expansion every 24 h. Significant cell engraftment/expansion was noted by greatly increased bioluminescence about 1 week posttransplant. Then PET was applied to acquire three-dimensional images of the whole-body in vivo biodistribution of the transplanted cells. To localize cells in the skeleton, PET was followed by computed tomography (CT). Co-registration of PET and CT mapped the sites of BM engraftment. Multiple, discrete BM cell engraftment sites were observed. Taken together, this multimodality approach may be useful for further in vivo characterization of various therapeutic cell types.
Sequential Bayesian learning of CDHMM based on finite mixture approximation of its prior/posterior density (2002)

Proposes a sequential Bayesian learning strategy of a continuous-density hidden Markov model (CDHMM) based on a finite mixture approximation of its prior/posterior density. The initial prior density of the CDHMM is assumed to be a finite mixture of natural conjugate prior probability density functions (PDFs) of the complete-data density. With the new observation data, the true posterior PDF is approximated by the same type of finite-mixture PDFs which retain the required most significant terms in the true posterior density according to their contribution to the corresponding Bayesian predictive density by using an N-best beam search algorithm. Then, the updated mixture PDF is used in the VBPC (Viterbi Bayesian predictive classification) method to deal with unknown mismatches in robust speech recognition. Experimental results on a speaker-independent recognition task of isolated Japanese digits confirm the viability and the usefulness of the proposed method.
Early vedolizumab trough levels at induction in inflammatory bowel disease patients with treatment failure during maintenance (2019)

We confirmed that a drug exposure-efficacy association was found early on at induction. This study emphasizes that previous exposure to anti-TNFα and positive perinuclear antineutrophil cytoplasmic antibody serology are important factors influencing VDZ TLs at induction.
Use of Substituted Bis(acetylacetone)ethylenediimine and Dialkyldithiocarbamate Ligands for Copper Chelation in Supercritical Carbon Dioxide (2006)

Chemical−mechanical planarization (CMP) is a process of oxidizing and chelating the copper overburden present in an interconnect device while mechanically polishing the surface of the wafer. Because the use of condensed CO2 as the solvent for CMP would be environmentally and technically advantageous, several substituted bis(acetylacetonate)ethylenediimine (R4BAE, where R = CH3 or CF3) and lithium or sodium dialkyldithiocarbamate (M+(R2DTC-), where M+ = Li+ or Na+ and R = ethyl, n-propyl, n-butyl, or 1,1,1-trifluoroethyl) ligands were used with t-butylperacetate (t-BuPA, as oxidant) for the oxidative dissolution of copper(0) in supercritical (sc) CO2 at 40 °C and 170−210 bar or in hexanes at 40 °C and atmospheric pressure. The reaction products from the copper etching were determined to be Cu(R4BAE) or Cu(R2DTC)2, respectively. The R2DTC- ligands had higher etch rates than the R4BAE ligands with comparable substituents, and the lithium dialkyldithiocarbamate salts gave higher copper etching rates than their sodium counterparts. The highest average etch rates were observed for Li((CF3CH2)2DTC): 16.7 nm/min in sc CO2 and 11.2 nm/min in hexanes. While hexanes have similar physical properties when compared to sc CO2, the rates of copper(0) removal with the R2DTC- ligands were 17−49% higher in sc CO2 than in hexanes at comparable temperatures and solvent densities. Scanning electron microscopy (SEM) images of the postreaction copper surfaces using the various ligands showed significant variations in surface roughness. X-ray photoelectron spectroscopy (XPS) measurements indicated that the lower R4BAE etch rates may be due to surface passivation by the R4BAE ligands and/or the Cu(R4BAE) complexes.
Aluminium amides derived from metallation of N,N′-di-tert-butylethylenediamine (1996)

The metallation of N,N′-di-tert-butylethylenediamine by AlH3·NMe3 has been investigated and shown to proceed via the formation of the unstable secondary amine-stabilised amidoalane [AlH2(ButNCH2CH2NButH)]. This compound reacted with an additional equivalent of AlH3·NMe3 to yield the dibridging amidoalane complex [(AlH2)2{µ-N(But)CH2CH2N(But)}] or a molecule of the diamine to give the triamidoaluminium species [Al(ButNCH2CH2NBut)(ButNCH2CH2NButH)]. In the absence of an excess of AlH3·NMe3 or N,N′-di-tert-butylethylenediamine, [AlH2(ButNCH2CH2NButH)] eliminates molecular hydrogen to give the trans isomer of the dimeric diamidoalane complex trans-[{AlH[µ-N(But)CH2CH2NBut]}2] which is stable toward reaction with either of the reactants. A stable analogue of the intermediate [AlH2(ButNCH2CH2NButH)] was made by replacing a hydride by a chloride, achieved by using AlH2Cl·NMe3 as the metallating agent. The cis isomer of the dimeric diamidoalane cis-[AlH{[µ-N(But)CH2CH2NBut]}2] was prepared from the unstable lithium diamido aluminium hydride species [{Li[N(But)CH2CH2NBut]AlH2}n]via elimination of lithium hydride. The aluminium triamide and the cis and trans isomers of the dimeric aluminium diamide have been structurally authenticated.
Growth of epitaxial 3C-SiC films on (111) silicon substrates at 850 °C by reactive magnetron sputtering (1993)

Reactive magnetron sputtering in a mixed Ar/CH4 discharge has been used to deposit 3C-SiC films on (111)-oriented Si substrates. The carbon content as well as the crystalline structure was found to depend on both the CH4 and Ar pressures. At a total pressure of 3 mTorr and a CH4 partial pressure of 0.6 mTorr, epitaxial stoichiometric films were obtained at growth temperatures as low as 850 °C. The epitaxial nature of the films was established by x-ray diffraction using a combination of reciprocal space maps, texture scans, and 360° φ scans. Based on these analyses it could also be concluded that double-positioning domains rotated 60° to one another as well as other defects, giving rise to a mosaic broadening in the reciprocal space maps, were present in the films. Furthermore, based on plasma probe measurements and determination of the electron energy distribution functions in the near-substrate vicinity, the low growth temperature of 850 °C is suggested to be a consequence of an effective decomposition of CH4 molecules in the plasma.
Ripple/dune to upper stage plane bed transition: Some observations from the ancient record (1992)

Abstract In two Proterozoic sandstones, of the Indian shield cross‐stratification and cross‐lamination are observed to grade continuously into parallel‐laminations often bearing parting lineations. These are interpreted as having resulted from a gradual transition from ripple/dune to upper stage plane bed structures. During the transition the inclination of the cross‐strata diminishes and their shape changes from concave‐up to sigmoidal. The sigmoidal cross‐strata are characterized by well defined topsets, foresets and toesets and the topsets bear parting lineations. In the course of the transition sigmoidal cross‐strata may give way either to horizontal parallel‐lamination or inclined parallel‐lamination. In the former the toesets of the successive sigmoidal cross‐strata thicken and the thickness of the cross‐strata beyond the brink point (the junction between the topset and foreset) tends to become uniform until a plane‐bed state is reached and horizontal parallel‐laminations are formed. In the latter the topset of the successive sigmoidal cross‐strata increases in length at the expense of the foreset and toeset until the brink point ceases to exist so that only the topset laminations prevail and appear as inclined parallel‐laminations. These transitions presumably result from a gradual increase in flow intensity beyond the stability limits of ripples/dunes. The progressive morphological changes of the cross‐stratification over the transition are attributed to changing fallout patterns on the lee face of the bedforms in response to increasing flow intensity. Preservation of the records of such transitions suggests an abundant supply of sand grade sediments from suspension during the transition, shaping the sediment concentration profile over the bedforms and facilitating turbulence suppression. The variation in the pattern of transition from sigmoidal cross‐stratification to parallel‐lamination may be the result of different rates of sediment feed from the prevailing suspended sediment load in the two instances.
Feasibility of Contactless Pulse Rate Monitoring of Neonates using Google Glass (2015)

In neonatal intensive care units in hospitals, vital signs of neonates are monitored continuously using wired sensors. However, these wired sensors introduce skin irritations, pain, discomfort and sleep disruptions for the neonates. State of the art camera-based vital sign algorithms are becoming popular as a solution to these issues. However, there are limited investigations into the feasibility of monitoring the neonates in a clinical setting with these algorithms. Also, recent emergence of a wide variety of wearable head-mounted devices, like Google Glass, enable vital sign monitoring to be ubiquitous. Again, feasibility of the use of such a device for vital sign monitoring is unknown. This paper investigates both the feasibility of using a camera-based algorithm for pulse rate monitoring of neonates in a clinical setting and the feasibility of using Google Glass for such pulse rate monitoring. The results of our research show under what conditions the monitoring of the pulse rate of neonates would be reliable and highlights the challenging conditions. Also, they give insights into the applicability of a Google Glass prototype for pulse rate monitoring and it’s current limitations.
Active Carboxylic Acid-Terminated Alkanethiol Self-Assembled Monolayers on Gold Bead Electrodes for Immobilization of Cytochromes c (2002)

It is extremely difficult to immobilize cytochrome c cyt c on carboxylic acid-terminated alkanethiol self-assembled monolayers HOOC-SAM on gold bead electrodes prepared in a hydrogen flame.We found that simple pretreatment of a HOOC-SAM/gold bead electrode by potential cycling in buffer solution in the range 300 mV prior to immobilization of the protein facilitated stable cyt c binding to HOOC-SAMs.The stability of cyt c on the HOOC-SAMs is independent of the topology of the gold surface.
Implementation of TSL Evaluations Beyond the Incoherent Approximation [Slides] (2022)

This presentation discusses the motivation behind the project, which is to facilitate the production of TSL libraries that contain high fidelity physics including coherent inelastic effects, such as graphite and beryllium. High fidelity TSL libraries are of interest in various applications, for example in relation to neutron scattering instrument response analysis and directional biases (reflection) in neutronic analysis. In summation, the removal of typical approximations, in terms of incoherent, cubic, and atom site are examined. The application of generalized equations to crystalline graphite and beryllium TSL evaluations and the validation of data and data formats is also discussed.
Temporal pattern of NFκB activation influences apoptotic cell fate in a stimuli-dependent fashion (2002)

The transcription factor NFkappaB is a critical immediate early response gene involved in modulating cellular responses and apoptosis following diverse environmental injuries. The activation of NFkappaB is widely accepted to play an anti-apoptotic role in cellular responses to injury. Hence, enhancing NFkappaB activation in the setting of injury has been proposed as one potential therapeutic approach to environmental injuries. To this end, we constructed a recombinant adenoviral vector (Ad.IkappaBalphaAS) expressing antisense IkappaBalpha mRNA that is capable of augmenting NFkappaB activation prior to and following four types of cellular injury [TNF-alpha, UV, hypoxia/reoxygenation (H/R) or pervanadate treatment]. Biochemical and functional analyses of NFkappaB activation pathways for these injuries demonstrated two categories involving either serine (S32/36) phosphorylation (TNF-alpha, UV) or tyrosine (Y42) phosphorylation (H/R or PV) of IkappaBalpha. We hypothesized that activation of NFkappaB prior to injury using antisense IkappaBalpha mRNA would reduce apoptosis. As anticipated, recombinant adenoviral IkappaBalpha phosphorylation mutants (Ad.IkappaBalphaS32/36A or Ad.IkappaBalphaY42F) preferentially reduced NFkappaB activation and enhanced apoptosis following injuries associated with either serine or tyrosine phosphorylation of IkappaBalpha, respectively. These studies demonstrate for the first time that an IkappaBalphaY42F mutant can effectively modulate NFkappaB-mediated apoptosis in an injury-context-dependent manner. Interestingly, constitutive activation of NFkappaB following Ad.IkappaBalphaAS infection reduced apoptosis only following injuries associated with IkappaBalpha Y42, but not S32/36, phosphorylation. These findings demonstrate that the temporal regulation of NFkappaB and the apoptotic consequences of this activation are differentially influenced by the pathway mediating NFkappaB activation. They also provide new insight into the therapeutic potential and limitations of modulating NFkappaB for environmental injuries such as ischemia/reperfusion and pro-inflammatory diseases.
A first‐in‐class, first‐in‐human, phase I trial of CIGB‐552, a synthetic peptide targeting COMMD1 to inhibit the oncogenic activity of NF‐κB in patients with advanced solid tumors (2021)

CIGB-552 is a synthetic peptide that interacts with COMMD1 and upregulates its protein levels. The objectives of this phase I study were safety, pharmacokinetic profile, evaluation of the lymphocytes CD4+ and CD8+ and preliminary activity in patients with advanced tumors. A 3 + 3 dose-escalation design with seven dose levels was implemented. Patients were included until a grade 3 related adverse event occurred and the maximum tolerated dose was reached. The patients received subcutaneous administration of CIGB-552 three times per week for 2 weeks. Single-dose plasma pharmacokinetics was characterized at two dose levels, and tumor responses were classified by RECIST 1.1. Twenty-four patients received CIGB-552. Dose-limiting toxicity was associated with a transient grade 3 pruritic maculopapular rash at a dose of 7.0 mg. The maximum tolerated dose was defined as 4.7 mg. Ten patients were assessable for immunological status. Seven patients had significant changes in the ratio CD4/CD8 in response to CIGB-552 treatment; three patients did not modify the immunological status. Stable disease was observed in five patients, including two metastatic soft sarcomas. We conclude that CIGB-552 at dose 4.7 mg was well tolerated with no significant adverse events and appeared to provide some clinical benefits.