gebhart/patrepeval huggingface dataset:
Study of hTERT and IL-12 DNA immunotherapy using electroporation in patients with solid tumors after definitive surgery and adjuvant therapy. (2015)

TPS3104 Background: hTERT, the human catalytic reverse transcriptase subunit of telomerase, is highly expressed in breast, lung, and pancreatic cancers. Peptides derived from hTERT can be recognized on MHC by cytotoxic T cells and mediate tumor death. In preclinical studies, TERT DNA delivered with electroporation (EP) triggered an immune response in vivo that slowed tumor growth in HPV16-associated tumor-bearing mice. The advantages of DNA-based immunotherapy include (1) strong immunogenicity exceeding those achieved by viral vectors; (2) non infectiousness of the immunogen; (3) ability for repeated dosing; and (4) relatively low cost. EP can be used to optimally and safely deliver DNA in vivo by creating a transient electric field to enhance the cellular uptake of large molecules such as DNA. Addition of IL-12 to hTERT significantly enhanced immune responses in preclinical models. We hypothesized that generation of robust T-cell immunity by immunotherapy with hTERT + IL-12 can be clinically used to reduce the risk of relapse in high-risk cancer patients in the adjuvant setting. Methods: This hypothesis is being tested in a phase 1 clinical trial (NCT02327468) sponsored by Inovio and opened at Abramson Cancer Center of the University of Pennsylvania. INO-1400 is a plasmid encoding hTERT. INO-9012 is a dual promoter plasmid encoding human IL-12 subunits p35 and p40. INO-1400 and INO-9012 are delivered IM followed by EP with the CELLECTRA device. This is an open-label, dose escalation study in patients with lung, pancreas, or breast carcinomas at high risk of relapse. Eligible patients must have early stage ER+ or HER2+, or any stage triple negative breast cancer; or Stage IB-IIIA NSCLC; or Stage I-III pancreatic cancer. Patients will enroll ≥ 4 and ≤ 16 weeks from completion of definitive surgery and adjuvant therapy into 1 of 6 cohorts (total N = 54): dosing INO-1400 at 2 or 8 mg ± INO-9012 at 0.5 or 2 mg, with EP, once every 4 weeks for 4 total treatments. Primary Endpoints:Safety and tolerability. Secondary Endpoints:(1) Time to progression; (2) Antigen-specific T cell response by IFN-γ ELISpot and flow cytometry; (3) antigen-specific humoral responses by ELISA. Clinical trial information: NCT02327468.
Transcriptional profiling by RNA-Seq of peri-attachment porcine embryos generated by a variety of assisted reproductive technologies (2013)

Substantial mortality of in vitro manipulated porcine embryos is observed during peri-attachment development. Herein we describe our efforts to characterize the transcriptomes of embryonic disc (ED) and trophectoderm (TE) cells from porcine embryos derived from in vivo fertilization, in vitro fertilization (IVF), parthenogenetic oocyte activation (PA), and somatic cell nuclear transfer (SCNT) on days 10, 12, and 14 of gestation. The IVF, PA, and SCNT embryos were generated with in vitro matured oocytes and were cultured overnight in vitro before being transferred to recipient females. Sequencing of cDNA from the resulting embryonic samples was accomplished with the Genome Analyzer IIx platform from Illumina. Reads were aligned to a custom-built swine transcriptome. A generalized linear model was fit for ED and TE samples separately, accounting for embryo type, gestation day, and their interaction. Those genes with significant differences between embryo types were characterized in terms of gene ontologies and KEGG pathways. Transforming growth factor-β signaling was downregulated in the EDs of IVF embryos. In TE cells from IVF embryos, ubiquitin-mediated proteolysis and ErbB signaling were aberrantly regulated. Expression of genes involved in chromatin modification, gene silencing by RNA, and apoptosis was significantly disrupted in ED cells from SCNT embryos. In summary, we have used high-throughput sequencing technologies to compare gene expression profiles of various embryo types during peri-attachment development. We expect that these data will provide important insight into the root causes of (and possible opportunities for mitigation of) suboptimal development of embryos derived from assisted reproductive technologies.
Differential Radiosensitization of Human Tumour Cells by 3-aminobenzamide and Benzamide: Inhibitors of Poly(ADP-ribosylation) (1986)

The effect of 3-aminobenzamide (3AB) and benzamide (BZ) (inhibitors of poly(ADP-ribose) synthetase) on radiosensitivity was investigated in normal human fibroblasts and three human cell lines established from tumours with varying degrees of clinical radiocurability. The human tumour cell lines selected were: Ewing's sarcoma, a bone tumour usually considered radiocurable with moderate radiation doses; lung adenocarcinoma, a tumour considered radiocurable with high doses of radiotherapy; and osteosarcoma, a very resistant tumour which is rarely controlled by standard doses of radiotherapy. Poly(ADP-ribose) synthetase inhibitors were added to cultures 2 h prior to irradiation and removed 24 h after. Inhibitors were used at doses producing little or no toxicity in cells. In the presence of these inhibitors, a differential radiosensitization was observed. Ewing's sarcoma cells and normal human fibroblasts were sensitized to an equal extent by either 8 mM 3AB or 4 mM BZ. However, no sensitization was observed at these concentrations in the lung adenocarcinoma cells or osteosarcoma cells. The degree of radiosensitization in vitro by 3AB and BZ correlates well with the clinical radiocurability of these tumours in vivo.
Role of ablation and incubation processes on surface nanograting formation (2011)

The role of ablation and incubation processes in the formation of surface nanogratings with femtosecond pulses were investigated by measuring ablation thresholds and depth of nanogrooves at different pulse to pulse spacings. Our observations indicated that the nanograting formation essentially relies on a laser ablation process which can be modeled by a simple set of equations.
Architecture and implementation of an associative memory using sparse clustered networks (2012)

Associative memories are alternatives to indexed memories that when implemented in hardware can benefit many applications such as data mining. The classical neural network based methodology is impractical to implement since in order to increase the size of the memory, the number of information bits stored per memory bit (efficiency) approaches zero. In addition, the length of a message to be stored and retrieved needs to be the same size as the number of nodes in the network causing the total number of messages the network is capable of storing (diversity) to be limited. Recently, a novel algorithm based on sparse clustered neural networks has been proposed that achieves nearly optimal efficiency and large diversity. In this paper, a proof-of-concept hardware implementation of these networks is presented. The limitations and possible future research areas are discussed.
Far Lateral Craniotomy for Resection of Foramen Magnum Meningioma (2019)

<b>Objective</b> Foramen magnum meningiomas present a formidable challenge to resection due to frequent involvement of the lower cranial nerves and vertebrobasilar circulation. The video shows the use of a far lateral craniotomy to resect a foramen magnum meningioma. <b>Design, Setting, and Participant</b> A 49-year-old woman presented with neck pain and was found to have a large foramen magnum meningioma ( Fig. 1A, B ). Drilling of the posterior occipital condyle was required to gain access to the lateral aspect of the brain stem. The amount of occipital condyle resection varies by patient and pathology. <b>Outcome/Result</b> Maximal total resection of the tumor was achieved ( Fig. 1B, C ), and the patient was discharged on postoperative day 4 with no neurologic deficits. The technique for tumor microdissection ( Fig. 2 ) is shown in the video. <b>Conclusion</b> Given the close proximity of foramen magnum meningiomas to vital structures at the craniocervical junction, surgical resection with careful microdissection and preservation of the overlying dura to prevent postoperative pseudomeningocele is necessary to successfully manage this pathology in those patients who are surgical candidates. The link to the video can be found at: https://youtu.be/Mds9N1x2zE0 .
Oncolytic virus synergizes with Smac mimetic compounds to induce rhabdomyosarcoma cell death in a syngeneic murine model (2016)

Rhabdomyosarcoma (RMS), a neoplasm characterized by undifferentiated myoblasts, is the most common soft tissue tumour in children. Therapeutic resistance is common in RMS and is often caused by acquired defects in the cellular apoptotic program. Smac mimetic compounds (SMCs) are a novel class of inhibitor of apoptosis (IAP) antagonists that are currently under clinical development as cancer therapeutics. We previously reported that cIAP1 is overexpressed in human primary RMS tumours and in patient-derived RMS cell lines where it drives resistance to apoptosis. In this study, we investigated whether inflammatory cytokine production triggered by activators of innate immunity synergizes with LCL161 to induce bystander killing of RMS cells in vitro and in vivo. Indeed, we show that innate immune stimuli (oncolytic virus (VSVΔ51-GFP), interferon γ (IFNγ), and tumour necrosis factor-like weak inducer of apoptosis (TWEAK)) combine with SMCs in vitro to reduce cell viability in the Kym-1 RMS cancer cell line. Other human RMS cell lines (RH36, RH41, RD, RH18, RH28, and RH30) and the murine RMS cell line 76-9 are resistant to treatment with LCL161 alone or in combination with immune stimulants in in vitro cell viability assays. In contrast, we report that the combination of LCL161 and VSVΔ51-GFP reduces tumour volume and prolongs survival in a 76-9 syngeneic murine model. Our results support further exploration of the combined use of IAP antagonists and innate immune stimuli as a therapeutic approach for RMS cancers.
Heavy Heparin: A Stable Isotope‐Enriched, Chemoenzymatically‐Synthesized, Poly‐Component Drug (2019)

Heparin is a highly sulfated, complex polysaccharide and widely used anticoagulant pharmaceutical. In this work, we chemoenzymatically synthesized perdeuteroheparin from biosynthetically enriched heparosan precursor obtained from microbial culture in deuterated medium. Chemical de-N-acetylation, chemical N-sulfation, enzymatic epimerization, and enzymatic sulfation with recombinant heparin biosynthetic enzymes afforded perdeuteroheparin comparable to pharmaceutical heparin. A series of applications for heavy heparin and its heavy biosynthetic intermediates are demonstrated, including generation of stable isotope labeled disaccharide standards, development of a non-radioactive NMR assay for glucuronosyl-C5-epimerase, and background-free quantification of in vivo half-life following administration to rabbits. We anticipate that this approach can be extended to produce other isotope-enriched glycosaminoglycans.
Anomaly Detection in Electrical Substation Circuits via Unsupervised Machine Learning (2016)

Cyber-physical systems (CPS), such as smart grids, include cyber assets for monitoring, control, and communication in order to maintain safe and efficient operation of a physical process. We propose that CPS intrusion detection systems (CPS IDS) should seek not just to detect attacks in the host audit logs and network traffic (cyber plane), but should consider how attacks are reflected in measurements from diverse devices at multiple locations (physical plane). In electric grids, voltage and current laws induce physical constraints that can be leveraged in distributed agreement algorithms to detect anomalous conditions. This can be done by explicitly coding the physical constraints into a hybrid CPS IDS, making the detector specific to a particular CPS. We present an alternative approach, along with preliminary results, using machine learning to characterize normal, fault, and attack states in a smart distribution substation CPS, using this as a component of a CPS IDS.
Two-dimensional fluorescence imaging of a flame-vortex interaction (1984)

Abstract The interaction of a methane-air flame with a vortex-ring structure was observed by means of quantitative imaging of the OH concentration using laser-induced fluorescence. The vortex-ring in the experiment was formed by an impulsive jet of gas exiting a thin-plate circular orifice separating a small cylindrical prechamber from the main combustion vessel. This impulsive jet was driven by a spark-ignited flame which propagates through the prechamber. The flame which exits the prechamber orifice follows in the wake of the vortex structure, and eventually overtakes it. A planar sheet of uv laser light from a Nd: YAG-pumped dye laser was used to excite fluorescence in the OH molecules produced by the flame. A two-dimensional image of the OH fluorescence was obtained with a gated image-intensified vidicon camera. The two-dimensional imaging results show the effect on the OH concentration distribution of fluid mechanic features of the vortex-ring structure: a wake flow with a shear layer, a stagnation-p...
Prospects for Conversion of Elemental Carbon from Fossil or Renewable Sources in Fuel Cells (2011)

Abstract not Available.
Xenopus oocyte K+ current. III. Phorbol esters and pH regulate current at gap junctions (1990)

Xenopus follicles consist of a single large oocyte surrounded by a monolayer of follicle cells attached to the oocyte by gap junctions. Adenosine 3',5'-cyclic monophosphate (cAMP) activates an outward K+ current which is completely abolished if follicle cells are removed or if phorbol esters (which have been reported to reduce gap junctional conductance) are added. In this study we show that phorbol esters do not reduce cAMP levels in follicles and that acid pH, another known stimulus for reducing gap junctional conductance, mimics the action of phorbol esters to inhibit the cAMP-stimulated K+ current. We also examined electrical coupling between oocytes of pairs of follicles placed in physical contact (across 2 oocyte-follicle cell and 1 follicle cell-follicle cell gap junction). Phorbol esters and acid pH (5.5-6.5) decreased electrical coupling without eliciting a shunt current, since slope conductance of current-voltage curves recorded during voltage clamp was simultaneously decreased. Increasing cAMP, which has been reported to enhance gap junctional conductance in mammalian cells, increased slope conductance without decreasing electrical coupling between pairs of follicles. The data suggest that cAMP increases and phorbol esters and acid pH decrease K+ currents at least in part by effects on gap junctions. The effects of phorbol esters and acid pH to reduce electrical coupling between oocytes cannot be due to blockade of K+ channels, since such an action would increase electrical coupling (as verified by computer simulations). These findings are consistent with the idea that cAMP-activated K+ currents originate in follicle cells and are communicated to the oocyte via gap junctions.
Dielectric and structural characterizations of La-Ti-O-N perovskite thin films (2012)

International audience
Single-Tube Analysis of DNA Methylation with Silica Superparamagnetic Beads (2010)

The MOB technique successfully combined 3 processes into a single tube, thereby allowing ease in handling and an increased detection throughput. The increased pre-PCR yield in MOB allowed efficient, diagnostically sensitive methylation detection.
Aberration-driven tilted emission in degenerate cavities (2023)

The compensation of chromatic dispersion opened new avenues and extended the level of control upon pattern formation in the \textit{temporal domain}. In this manuscript, we propose the use of a nearly-degenerate laser cavity as a general framework allowing for the exploration of higher contributions to diffraction in the \textit{spatial} domain. Our approach leverages the interplay between optical aberrations and the proximity to the self-imaging condition which allows to cancel or reverse paraxial diffraction. As an example, we show how spherical aberrations materialize into a transverse bilaplacian operator and, thereby, explain the stabilization of temporal solitons travelling off-axis in an unstable mode-locked broad-area surface-emitting laser. We disclose an analogy between these regimes and the dynamics of a quantum particle in a double well potential.
Phase II Trial of Combination of Bortezomib and Rituximab in Relapsed and/or Refractory Waldenstrom Macroglobulinemia: Preliminary Results. (2007)

Abstract INTRODUCTION: Previous studies have demonstrated the clinical activity of bortezomib as a single agent in patients with Waldenstrom Macroglobulinemia (WM). We performed preclinical studies that demonstrated synergistic activity of bortezomib with the anti-CD20 antibody rituximab in WM cell lines. This phase II study aimed to determine safety and activity of weekly bortezomib in combination with rituximab in patients with relapsed/refractory WM. METHODS: Patients who had at least one previous therapy for WM, symptomatic, and who had relapsed or refractory disease were eligible. NCI CTCAE v3.0 was used for toxicity assessment. Response was assessed by criteria established at the second consensus panel for WM. All patients received bortezomib IV weekly at 1.6mg/m2 on days 1, 8, 15 q 28 days x 6 cycles and rituximab 375 mg/m2 at days 1, 8, 15, 22 on cycles 1 and 4. RESULTS: 17 pts (10 men and 7 women, median age 62 years, range 43 – 81) have been treated to date. The median number of lines of prior treatment was 3 (range 1 – 5) including prior bortezomib and prior rituximab in some of those patients. The median IgM at baseline was 4070 mg/dL (range 1370– 10,800); median M-spike at baseline was 2.48 g/dL (range 1.5 – 4.87); and median hemoglobin was 11.0 g/dL (6.3–15.2). The median follow up was 5 months (range 1 – 11 months). Prior therapy included rituximab, nucleoside analogues (fludarabine and 2-CDA), combination chemotherapy (e.g CHOP, CVP), chlorambucil, and bortezomib. 13 pts are currently evaluable for response, best response to bortezomib and rituximab after 2 cycles are presented in Table 1. Median duration of response has not been reached. None of the patients progressed while on therapy with bortezomib and rituximab. Patients tolerated therapy well without significant toxicities: grade 3 peripheral neuropathy occurred in only 1 patient at cycle 6 and improved to grade 1 within 2 weeks of holding therapy. Other grade 3 and 4 toxicities included neutropenia in 3 patients, and anemia and hyponatremia in 1 patient. One patient discontinued therapy on study after 1 cycle because of inability to travel to study site and completed similar treatment off study and was unevaluable on this study. Attributable toxicities otherwise proved manageable with appropriate supportive care and the combination was generally well tolerated. CONCLUSIONS: The combination of weekly bortezomib and rituximab has been well tolerated and demonstrates exciting activity achieving CR+ PR + MR in 85%, and/or stabilization of disease in 15% of evaluable patients with relapsed WM. No significant peripheral neuropathy was observed with this regimen. Updated data will be presented at the meeting. Response N=13; ORR (CR+PR+MR)= 85% Median time to best response (months) Complete Response 1 (8%) 6 Partial Response 3 (23%) 3.5 (3–4) Minimal Response 7 (54%) 4 (2–6) Stable Disease 2 (15%) NA Progressive Disease 0
Applications of SOAs in Optical Access and Metro Networks (2001)

We will discuss experimental local and metropolitan area networks which employ semiconductor optical amplifiers (SOA). The talk will cover a range of architectures including point-point metro DWDM using cascaded SOAs, transparent metro WDM rings, and local star architectures.
Targeting type-2 metabotropic glutamate receptors to protect vulnerable hippocampal neurons against ischemic damage (2015)

These findings suggest that the mGlu2 receptor is an important player in mechanisms regulating neuronal vulnerability to ischemic damage, and that mGlu2 receptor NAMs are potential candidates in the experimental treatments of disorders characterized by brain hypoperfusion, such as hypovolemic shock and cardiac arrest.
Modular Peptide Growth Factors for Substrate‐Mediated Stem Cell Differentiation (2009)

Die Sequenzspezifität beim Binden eines modularen Peptidwachstumsfaktors (eBGa3) mit einer von BMP2 abgeleiteten Sequenz und einer durch Osteocalcin inspirierten Mineralbindesequenz an Ca-Ionen von Hydroxyapatit (HA) ist vermutlich teilweise auf die Entwicklung einer α-helicalen Struktur in Gegenwart von HA zurückzuführen, durch die γ-carboxylierte Glutaminsäurereste im Peptid (cyan) von Ca-Atomen (orange) im HA-Kristallgitter registriert werden können.
Stimulation of DNA synthesis and c-fos expression in corneal endothelium by insulin or insulin-like growth factor-I. (1993)

The number of insulin-like growth factor-I receptors far exceeds the number of insulin receptors in bovine corneal endothelium, suggesting that the effects of insulin on c-fos gene expression and mitogenesis were likely to be mediated through the insulin-like growth factor-I receptor.
Ack1 Mediated AKT/PKB Tyrosine 176 Phosphorylation Regulates Its Activation (2020)

The AKT/PKB kinase is a key signaling component of one of the most frequently activated pathways in cancer and is a major target of cancer drug development. Most studies have focused on its activation by Receptor Tyrosine Kinase (RTK) mediated Phosphatidylinositol-3-OH kinase (PI3K) activation or loss of Phosphatase and Tensin homolog (PTEN). We have uncovered that growth factors binding to RTKs lead to activation of a non-receptor tyrosine kinase, Ack1 (also known as ACK or TNK2), which directly phosphorylates AKT at an evolutionarily conserved tyrosine 176 in the kinase domain. Tyr176-phosphorylated AKT localizes to the plasma membrane and promotes Thr308/Ser473-phosphorylation leading to AKT activation. Mice expressing activated Ack1 specifically in the prostate exhibit AKT Tyr176-phosphorylation and develop murine prostatic intraepithelial neoplasia (mPINs). Further, expression levels of Tyr176-phosphorylated-AKT and Tyr284-phosphorylated-Ack1 were positively correlated with the severity of disease progression, and inversely correlated with the survival of breast cancer patients. Thus, RTK/Ack1/AKT pathway provides a novel target for drug discovery.