gebhart/patrepeval huggingface dataset:
Data from Intra–Lymph Node Prime-Boost Vaccination against Melan A and Tyrosinase for the Treatment of Metastatic Melanoma: Results of a Phase 1 Clinical Trial (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; The goal of this study was to test the safety and activity of a therapeutic vaccine, MKC1106-MT, in patients with metastatic melanoma.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; MKC1106-MT comprises a plasmid (pMEL-TYR) and two peptides (E-MEL and E-TYR), corresponding to Melan A and tyrosinase, administered by intra–lymph node injection in a prime-boost sequence. All 18 patients were HLA-A*0201 positive and received a fixed priming dose of plasmid and a low or a high peptide dose. Enumeration of antigen-specific T cells was done prior to and throughout the treatment. Patients who did not exhibit disease progression remained on study and could receive up to eight cycles of treatment.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; The MKC1106-MT regimen was well tolerated and resulted in an overall immune response rate of 50%. The treatment showed disease control, defined as stable disease that lasted for 8 weeks or more in 6 of 18 (33%) of the patients: 14% and 46% in the low and high peptide dose, respectively. Interestingly, four patients, all with tumor burden largely confined to lymph nodes and Melan A–specific T cells at baseline, showed durable disease control associated with radiologic evidence of tumor regression. There was no noticeable correlation between the expansion of antigen-specific T cells in blood and the clinical outcome; yet, there was evidence of active tumor-infiltrating lymphocytes (TIL) in two regressing lesions.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; MKC1106-MT showed immunogenicity and evidence of disease control in a defined patient population. These findings support further development of this investigational agent and the concept of therapeutic vaccination in metastatic melanoma. &lt;i&gt;Clin Cancer Res; 17(9); 2987–96. ©2011 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
A simple mechanism to adapt leakage-control policies to temperature (2005)

Leakage power reduction in cache memories continues to be a critical area of research because of the promise of a significant pay-off. Various techniques have been developed so far that can be broadly categorized into state-preserving (e.g., Drowsy Caches) and non-state preserving (e.g., Cache Decay). Decay saves more leakage but also incurs dynamic power overhead in the form of induced misses. Previous work has shown that depending on the leakage vs. dynamic power trade-off, one or the other technique can be better. Several factors such as cache architecture, technology parameters and temperature, affect this trade-off. Our work proposes the first mechanism ---to the best of our knowledg--- that takes into account temperature in adjusting the leakage control policy at run time. At very low temperatures, leakage is relatively weak so the need to tightly control it is not as important as the need to minimize extra dynamic power (e.g., decay-induced misses) or performance loss. We use a hybrid decay+drowsy policy where the main benefit comes from decaying cache lines while the drowsy mode is used to save leakage in long decay intervals. To adapt the decay mode to temperature, we propose a simple triggering mechanism that is based on the principles of decaying 4T thermal sensors and, as such, tied to temperature. The hotter the cache is, the faster cache lines are decayed since it is beneficial to do so with very high leakage currents.Conversely, when the cache temperature is low, our mechanism defers putting cache lines in decay mode to avoid dynamic power overhead but still saves a significant amount of leakage using the drowsy mode. Our study shows that across a wide range of temperatures, the simple adaptability of our proposal yields consistently better results than either the decay mode, or drowsy mode alone, improving over the best by as much as 33%
Association between sialyl Lewis(a) expression and tumor progression in melanoma. (1995)

Twenty-three primary and 27 metastatic melanoma lesions and 17 pigmented nevi lesions were tested utilizing the immunoperoxidase reaction with anti-sialyl Lewis(a) (sLea) and anti-sLex mAbs.sLea was expressed in 9, 25, and 5 and sLex was expressed in 6, 11, and 2 of these lesions, respectively. Expression of sLea in melanocytic tumors is associated with tumor progression. Serum levels of sLea and sLex were analyzed by a sandwich assay using mAbs in 25 melanoma patients. Only 2 patients at stage 4 showed higher levels of sLea and sLex than did normal control subjects. Moreover, sLea and sLex were expressed in 1 and 2 of 5 human melanoma cell lines, respectively, and expression of sLex and sLex was not modulated by cytokines. These findings suggest that the expression of sLea in melanocytic tumors is correlated with disease progression.
744 Multi-armed myxoma virus has therapeutic potential for treatment of multiple myeloma (2021)

<h3>Background</h3> Despite improvements with new therapeutics, multiple myeloma (MM) patients still relapse and become refractory. Myxoma virus (MYXV) selectively replicates in human tumor cells and stimulates the immune system. MYXV selectively kills human patient MM cells and spares normal progenitors. MYXV also eradicates growth of a disseminated mouse MM in vivo. MYXV is a large, double stranded DNA poxvirus, and has a genome size amenable to insertion of multiple transgenes. We generated MYXV carrying IL-12 and decorin. IL-12 is an immune modulator that activates T- and NK-cells. Cellular responses to decorin include tumor cell intrinsic signaling effects, tumor matrix modulation, and inhibition of the TGF-beta pathway. This represents a promising therapeutic option for MM patients that do not respond well to immunotherapy. The current work suggests MYXV armed with IL-12 and decorin could be an effective anti-MM therapy. <h3>Methods</h3> Cytotoxicity assays were performed using a cell viability assay. Transgene expression levels were analyzed by microscopy, flow cytometry, and ELISA. <h3>Results</h3> Human MM cell line U266 infected with MYXV (vMYX-hIL-12/Dec) carrying human IL-12, decorin, and green fluorescent protein (GFP) produced transgenes in a dose and time responsive manner. A panel of human MM cell lines was infected with vMYX-hIL-12/Dec and transgene expression in supernatant, cell killing EC50, and GFP levels were evaluated. Sensitive and resistant human MM cell lines were identified. The comparison of replication, cell killing capacity, and transgene expression highlighted the independent importance of these mechanisms in overall activity. <h3>Conclusions</h3> The current work describes the oncolytic activity and transgene expression following exposure to vMYX-hIL-12/Dec in human MM cell lines in vitro. Our initial studies suggest there is significant value in pursuing vMYX-hIL-12/Dec and other armed MYXV as a new approach towards MM therapy.
Improving Localization of Deep Inclusions in Time-Resolved Diffuse Optical Tomography (2019)

Time-resolved diffuse optical tomography is a technique used to recover the optical properties of an unknown diffusive medium by solving an ill-posed inverse problem. In time-domain, reconstructions based on datatypes are used for their computational efficiency. In practice, most used datatypes are temporal windows and Fourier transform. Nevertheless, neither theoretical nor numerical studies assessing different datatypes have been clearly expressed. In this paper, we propose an overview and a new process to compute efficiently a long set of temporal windows in order to perform diffuse optical tomography. We did a theoretical comparison of these large set of temporal windows. We also did simulations in a reflectance geometry with a spherical inclusion at different depths. The results are presented in terms of inclusion localization and its absorption coefficient recovery. We show that (1) the new windows computed with the developed method improve inclusion localization for inclusions at deep layers, (2) inclusion absorption quantification is improved at all depths and, (3) in some cases these windows can be equivalent to frequency based reconstruction at GHz order.
Effects of flow rate on transnasal pulmonary aerosol delivery of bronchodilators via high-flow nasal cannula for patients with COPD and asthma: protocol for a randomised controlled trial (2019)

NCT03739359; Pre-results.
On the Design of Differential Kronecker Product Beamformers (2021)

In this paper, we present a generalized approach for differential microphone array (DMA) beamforming in the short-time Fourier transform (STFT) domain. We propose a multistage beamforming approach, which considers a Kronecker product (KP) decomposition of the global beamformer into two independent sub-beamformers. We derive differential KP beamformers according to different criteria and analyze their performances, which are tuned by three design parameters. These parameters allow a high beamforming design flexibility; in particular, non-differential or non-KP beamformers may be obtained as special cases. Depending on the selection of parameters, we demonstrate a preferable performance with the new approach with respect to the white noise gain and directivity factor measures. In addition, we consider the task of speech enhancement. We show that differential KP beamformers perform better than non-differential and non-KP beamformers in terms of the quality and intelligibility of their respective time-domain enhanced signals, particularly in moderately reverberant environments.
Site-specific incorporation of 4-Iodo-l-phenylalanine through opal suppression (2010)

A variety of unique codons have been employed to expand the genetic code. The use of the opal (UGA) codon is promising, but insufficient information is available about the UGA suppression approach, which facilitates the incorporation of non-natural amino acids through suppression of the UGA codon. In this study, the UGA codon was used to incorporate 4-iodo-l-phenylalanine into position 32 of the Ras protein in an Escherichia coli cell-free translation system. The undesired incorporation of tryptophan in response to the UGA codon was completely repressed by the addition of indolmycin. The minor amount (3%) of contaminating 4-bromo-l-phenylalanine in the building block 4-iodo-l-phenylalanine led to the significant incorporation of 4-bromo-l-phenylalanine (21%), and this problem was solved by using a purified 4-iodo-l-phenylalanine sample. Optimization of the incubation time was also important, since the undesired incorporation of free phenylalanine increased during the cell-free translation reaction. The 4-iodo-l-phenylalanine residue can be used for the chemoselective modification of proteins. This method will contribute to advancements in protein engineering studies with non-natural amino acid substitutions.
A Facile Synthesis of N- and O-alkylated Nicotinonitriles and its 2-methoxy 1,2,3-triazole Candidates as Potential Anticancer and Antimicrobial Agents (2018)

A series of N- and O- alkylated nicotinonitriles was reported. Base mediate alkylation of nicotinonitriles 1a-c with chloroacetonitrile, allyl bromide and propargyl bromide produced N- and O- alkylated nicotinonitrile derivatives 3-6. Reaction of compounds 6a,b with ethyl 2- azidoacetate in the presence of CuSO4 and sodium ascorbate afforded 1,4-disubstituted triazoles 7a,b. The anticancer activity against RPE-1 and MCF-7 human cell lines showed that all compounds did not showed big variation in their cytotoxicity activities at concentrations of 25, 50 and 100 μM against both cell types. The antimicrobial activity of the new compounds showed that all the tested compounds do not showed significant antibacterial and antifungal activities against the mention microorganisms, except compounds 4b, 5c, 5d and 6b showed moderate antimicrobial activity towards Bacillus subtilis.
A Novel Dual Channel MAC Protocol for IEEE802.11 Ad-Hoc Networks (2006)

In this paper, we propose a link-directionality-based dual channel MAC protocol in an attempt to double the capacities of networks using the single-channel 802.11 protocol. Simulations show that the proposed scheme can achieve more than 78% of our targeted capacities. We believe this is a first paper in the literature to propose a MAC protocol to transmit RTS/DATA and CTS/ACK of a link in different channels. This yields a large potential for multiplying the network capacities of ad-hoc networks by using only two channels.
Generation of Avian Cells Resembling Osteoclasts from Mononuclear Phagocytes* (1991)

Several lines of indirect evidence suggest that a monocyte family precursor gives rise to the osteoclast, although this hypothesis is controversial. Starting with a uniform population of nonspecific esterase positive, tartrate-sensitive, acid phosphatase-producing, mannose receptor-bearing mononuclear cells, prepared from dispersed marrow of calcium-deprived laying hens by cell density separation and selective cellular adherence, we generated multinucleated cells in vitro. When cultured with devitalized bone, these cells show, by electron microscopy, the characteristic osteoclast morphology in that they are mitochondria-rich, multinucleated, and, most importantly, develop characteristic ruffled membranes at the matrix attachment site. Moreover, as documented by scanning electron microscopy, these cells pit bone slices in a manner identical to freshly isolated osteoclasts. In addition, isoenzymes of acid phosphatase from generated osteoclasts, separated by 7.5% polyacrylamide gel electrophoresis at pH 4, are identical to those of mature osteoclasts in migration pattern and tartrate resistance, although the precursor cells from which the osteoclasts are generated produce an entirely different isoenzyme, which is tartrate-sensitive and migrates less rapidly at pH 4. The fused cells also exhibit a cAMP response to prostaglandin E2. Therefore, osteoclast-like cells can be derived by in vitro culture of a marrow-derived monocyte cell population.
Rapamycin rescues BMP mediated midline craniosynostosis phenotype through reduction of mTOR signaling in a mouse model (2018)

Summary Craniosynostosis is defined as congenital premature fusion of one or more cranial sutures. While the genetic basis for about 30% of cases is known, the causative genes for the diverse presentations of the remainder of cases are unknown. The recently discovered cranial suture stem cell population affords an opportunity to identify early signaling pathways that contribute to craniosynostosis. We previously demonstrated that enhanced BMP signaling in neural crest cells (caA3 mutants) leads to premature cranial suture fusion resulting in midline craniosynostosis. Since enhanced mTOR signaling in neural crest cells leads to craniofacial bone lesions, we investigated the extent to which mTOR signaling is involved in the pathogenesis of BMP‐mediated craniosynostosis by affecting the suture stem cell population. Our results demonstrate a loss of suture stem cells in the caA3 mutant mice by the newborn stage. We have found increased activation of mTOR signaling in caA3 mutant mice during embryonic stages, but not at the newborn stage. Our study demonstrated that inhibition of mTOR signaling via rapamycin in a time specific manner partially rescued the loss of the suture stem cell population. This study provides insight into how enhanced BMP signaling regulates suture stem cells via mTOR activation.
A 500-MHz Sigma-Delta Phase-Interpolation Direct Digital Synthesizer (2007)

International audience
Meningococcal Disease in the Netherlands, 1958-1990: A Steady Increase in the Incidence Since 1982 Partially Caused by New Serotypes and Subtypes of Neisseria meningitidis (1993)

In order to explain a threefold increase in the incidence of meningococcal disease in the Netherlands during the 1980s, we serotyped and subtyped Neisseria meningitidis isolates recovered between 1958 and 1990 from > 3,000 patients with systemic disease. No single strain could be held responsible for the increase. Apart from the newly introduced strain B:4:P1.4, which became the most prevalent phenotype in 1990 (21% of all isolates), the majority of the cases in 1990 were caused by many different strains that were already present in the Netherlands before 1980. For the period 1980-1990, a shift in the age distribution of patients with meningococcal disease from younger to older age categories was found, particularly with regard to cases due to meningococci of serogroup B; this shift is explained by the changing distribution of serotypes and subtypes within serogroup B. A polyvalent group B, class 1 outer-membrane-protein vaccine of a stable composition could theoretically have prevented approximately 80% of all group B meningococcal infections in the Netherlands during the past 30 years.
854 HPK1 inhibition relieves suppression downstream of TCR activation to drive enhanced cytokine production and antigen-specific killing, an effect that is further enhanced by immune checkpoint blockade (2022)

<h3>Background</h3> T cell activation is critical in the initiation and potentiation of anti-tumor immune responses. Hematopoietic Progenitor Kinase 1 (HPK1) is a member of the MAP4K family whose activity restrains T cell activation through phosphorylation of SLP-76 (pSLP-76) at Serine 376, leading to disassembly of the TCR complex. Mouse genetic deletion and kinase dead mutants of HPK1 have been shown to enhance T cell activity and combine with immune checkpoint inhibition. Therefore, we sought to demonstrate that inhibitors of HPK1 activity can increase T cell activation, drive antigen-specific cancer cell killing, and combine with immune checkpoint blockade to amplify anti-tumor T cell responses. Herein, we describe the characterization of novel inhibitors of HPK1 and assess their effects on T cell activation in combination with PD-1 blockade. <h3>Methods</h3> Measurement of pSLP-76 using a flow cytometry-based assay was employed to assess HPK1 activity in human and mouse whole blood. Jurkat cells, human CD8<sup>+</sup> T cells and PBMCs were activated using anti-CD3/CD28 stimulation, CEF peptide pools, or Staphylococcal enterotoxin A (superantigen), in the presence of HPK1 inhibitors; levels of IL-2, IFN-γ and TNF-α were assayed in supernatants by cytokine bead array. Mouse OT-1 splenocytes were stimulated with SIINFEKL peptide and co-cultured with E.G7-OVA cells to assess cytokine production and target cell killing. <h3>Results</h3> HPK1 inhibitors exhibited a potent, concentration-dependent reduction in pSLP-76, with a concurrent increase in IL-2 secretion in both Jurkat and human CD8<sup>+</sup> T cells. Human T cells also demonstrated increased IFN-γ and TNF-α secretion as well as a greater percentage of activated CD69<sup>+</sup> cells with HPK1 inhibition. These increases in T cell activation were mirrored in antigen-specific OT-1 T cell assays, in which HPK1 inhibition enhanced IFN-γ production in response to OVA peptide and greater killing of E.G7-OVA cancer cells. Similarly, antigen-recall assays demonstrated that inhibition of HPK1 increased IFN-γ production from human PBMC stimulated with CEF peptide and combined with PD-1 blockade to further enhance cytokine production. Consistent with these results, HPK1 inhibition and PD-1 blockade increased cytokine secretion in superantigen-stimulated human PBMC individually and further enhanced cytokine production in combination. Taken together, these data demonstrate that the combined activity of HPK1 inhibition with checkpoint therapy may yield greater anti-tumor T cell activity. <h3>Conclusions</h3> These data demonstrate that pharmacological inhibition of HPK1 amplifies antigen-specific T cell activation alone or in combination with immune checkpoint blockade and provide a strong mechanistic rationale for targeting HPK1 to amplify anti-tumor immune responses.
Liquid Chromatography–Tandem Mass Spectrometry Assay of Leukocyte Acid α-Glucosidase for Post-Newborn Screening Evaluation of Pompe Disease (2017)

This assay allows determination of low residual GAA activity in leukocytes. IOPD, LOPD, and pseudodeficiency patients can be partially differentiated by measuring GAA using blood samples.
Channel-Reconstruction-Based Hybrid Precoding for Millimeter-Wave Multi-User MIMO Systems (2018)

The focus of this paper is on multi-user multi-input multi-output transmissions for millimeter-wave systems with a hybrid precoding architecture at the base station. To enable multiuser transmissions, the base station uses a cell-specific codebook of beamforming vectors over an initial beam alignment phase. Each user uses a user-specific codebook of beamforming vectors to learn the top-P (where P ≥ 1) beam pairs in terms of the observed signal-to-noise ratio (SNR) in a single-user setting. The top-P beam indices along with their SNRs are fed back from each user and the base station leverages this information to generate beam weights for simultaneous transmissions. A typical method to generate the beam weights is to use only the best beam for each user and either steer energy along this beam, or to utilize this information to reduce multi-user interference. The other beams are used as fallback options to address blockage or mobility. Such an approach completely discards information learned about the channel condition(s) even though each user feeds back this information. With this background, this paper develops an advanced directional precoding structure for simultaneous transmissions at the cost of an additional marginal feedback overhead. This construction relies on three main innovations: first, additional feedback to allow the base station to reconstruct a rank-P approximation of the channel matrix between it and each user; second, a zero-forcing structure that leverages this information to combat multi-user interference by remaining agnostic of the receiver beam knowledge in the precoder design; and third, a hybrid precoding architecture that allows both amplitude and phase control at low complexity and cost to allow the implementation of the zero-forcing structure. Numerical studies show that the proposed scheme results in a significant sum rate performance improvement over naive schemes even with a coarse initial beam alignment codebook.
Investigations of chemical vapor deposition of GaN using synchrotron radiation (2000)

The authors apply synchrotron x-ray analysis techniques to probe the surface structure of GaN films during synthesis by metal-organic chemical vapor deposition (MOCVD). Their approach is to observe the evolution of surface structure and morphology in real time using grazing incidence x-ray scattering (GIXS). This technique combines the ability of x-rays to penetrate the chemical vapor deposition environment for in situ measurements, with the sensitivity of GIXS to atomic scale structure. In this paper they present examples from some of their studies of growth modes and surface evolution as a function of process conditions that illustrate the capabilities of synchrotron x-ray analysis during MOCVD growth. They focus on studies of the homoepitaxial growth mode, island coarsening dynamics, and effects of impurities.
Pharmacokinetic and clinical profile of a novel formulation of bosentan in children with pulmonary arterial hypertension: the FUTURE‐1 study (2009)

Exposure to bosentan, as shown comparing the results from this study with those from a study in adults, was different in paediatric and adult PAH patients. Since FUTURE-1 and past studies suggest a favourable benefit-risk profile for bosentan at 2 mg kg(-1) b.i.d., this dose is recommended for children with PAH. The new paediatric formulation was well tolerated.