gebhart/patrepeval huggingface dataset:
Rituximab plus gemcitabine and oxaliplatin (R-GemOx) in refractory/relapsed diffuse large B-cell lymphoma: a real-life study in patients ineligible for autologous stem-cell transplantation (2021)

There is no established standard treatment for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in patients who are not eligible to receive an intensive treatment. The combination of rituximab gemcitabine and oxaliplatin (R-GemOx) is widely used in this population but data are scarce. We retrospectively collected the data of 196 patients with R/R DLBCL treated with R-GemOx in two French centers over a period of 15 years. The median age of the population was 72 years (range, 24-89), 63% of the patients had an international prognostic index of 3 or higher and 57% were refractory to the last treatment. At the end of R-GemOx treatment, 33% of the patients obtained a complete response. The median progression-free survival (PFS) of the population was 5 months and the median overall survival (OS) was 10 months. Several factors were predictors of unfavorable survival: age over 75 years, international prognostic index of 2 or higher, refractory disease and de novo DLBCL. The median PFS and OS of the patients who obtained a complete response were 22 months and 40 months, respectively. The most significant toxicities were grade 3-4 hematological toxicities (31% of patients). Given its efficacy and tolerability, R-GemOx can be used in patients ineligible for intensive treatment and serve as a basis for new regimen combinations.
Supramolecular Polymerization of a Photo-Fluttering Chiral Monomer: A Temporarily Suspendable Chain Growth by Light (2022)

Using a photochemically fluttering thiophene-fused cyclooctatetraene derivative (<b>COT</b>) as a nonplanar chiral monomer, we have succeeded in remotely suspending the supramolecular polymerization in a temporal manner by a completely new strategy. The <b>COT</b> monomer with an 8π electron core adopts a saddle shape in the ground state and flutters 5.8 × 10<sup>3</sup> times faster upon photoirradiation than in the dark as a result of the stabilized planar conformation by the excited-state aromaticity (Baird aromaticity). Detailed investigation revealed that without photoirradiation the rate constant of the fluttering motion is 1/560 times smaller than that of the chain elongation, indicating that the fluttering of <b>COT</b> does not affect the chain elongation in the dark. In contrast, under photoirradiation (365 nm), the fluttering of <b>COT</b> is at least 11 times more rapid than the chain elongation, thereby suppressing the elongation event. The rapid fluttering of <b>COT</b> to suspend the chain elongation is not accompanied by a decrease in active monomer concentration, leading to depolymerization.
A Carbocyclic Curcumin Inhibits Proliferation of Gram-Positive Bacteria by Targeting FtsZ (2016)

Inhibition of FtsZ assembly has been found to stall bacterial cell division. Here, we report the identification of a potent carbocyclic curcumin analogue (2d) that inhibits Bacillus subtilis 168 cell proliferation by targeting the assembly of FtsZ. 2d also showed potent inhibitory activity (minimum inhibitory concentrations of 2-4 mg/L) against several clinically important species of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. In addition, 2d displayed a significantly reduced inhibitory effect on human cervical cancer cells in comparison to its effect on bacterial cells. Using live cell imaging of GFP-FtsZ by confocal microscopy, 2d was found to rapidly perturb the cytokinetic FtsZ rings in Bacillus subtilis cells. The immunofluorescence imaging of FtsZ also showed that 2d destroyed the Z-ring in bacteria within 5 min. Prolonged treatment with 2d produced filamentous bacteria, but 2d had no detectable effect either on the nucleoids or on the membrane potential of bacteria. 2d inhibited FtsZ assembly in vitro, whereas it had minimal effects on tubulin assembly. Interestingly, 2d strongly enhanced the GTPase activity of FtsZ and reduced the GTPase activity of tubulin. Furthermore, 2d bound to purified FtsZ with a dissociation constant of 4.0 ± 1.1 μM, and the binding of 2d altered the secondary structures of FtsZ. The results together suggested that the non-natural curcumin analogue 2d possesses powerful antibacterial activity against important pathogenic bacteria, and the evidence indicates that 2d inhibits bacterial proliferation by targeting FtsZ.
Fantastic beasts and how to sequence them: genomic approaches for obscure model organisms (2017)

Summary Application of genomic approaches to “obscure model organisms” (OMOs), meaning species with little or no genomic resources, enables increasingly sophisticated studies of genomic basis of evolution, acclimatization and adaptation in real ecological contexts. Here, I highlight sequencing solutions and data handling techniques most suited for genomic analysis of OMOs. Glossary - Allele Frequency Spectrum, AFS (same as Site Frequency Spectrum, SFS): histogram of the number of segregating variants depending on their frequency in one or more populations. - Restriction site-Associated DNA (RAD) sequencing : family of diverse genotyping methods that sequence short fragments of the genome adjacent to recognition site(s) for specific restriction endonuclease(s). - Linkage Disequilibrium (LD) : in this review, correlation of genotypes at a pair of markers across individuals. - LD block : typical distance between markers in the genome across which their genotypes remain correlated. - Genome scan: profiling of genotypes along the genome looking for unusual patterns. Often used to look for signatures of natural selection or introgression. - “Denser-than-LD” genotyping : genotyping of several polymorphic markers per LD block. - Highly contiguous reference : genome or transcriptome reference sequence containing the least amount of fragmentation. - Phased data : data showing which SNP alleles belong to the same homologous chromosome copy. - Cross-tissue gene expression analysis : looking for individual-specific shifts in gene expression detectable across multiple tissues. Such shifts are predominantly genetic in nature.
Discovery of Potent and Specific Fructose-1,6-Bisphosphatase Inhibitors and a Series of Orally-Bioavailable Phosphoramidase-Sensitive Prodrugs for the Treatment of Type 2 Diabetes (2007)

Excessive glucose production by the liver coupled with decreased glucose uptake and metabolism by muscle, fat, and liver results in chronically elevated blood glucose levels in patients with type 2 diabetes. Efforts to treat diabetes by reducing glucose production have largely focused on the gluconeogenesis pathway and rate-limiting enzymes within this pathway such as fructose-1,6-bisphosphatase (FBPase). The first potent FBPase inhibitors were identified using a structure-guided drug design strategy (Erion, M. D.; et al. J. Am. Chem. Soc. 2007, 129, 15480-15490) but proved difficult to deliver orally. Herein, we report the synthesis and characterization of a series of orally bioavailable FBPase inhibitors identified following the combined discoveries of a low molecular weight inhibitor series with increased potency and a phosphonate prodrug class suitable for their oral delivery. The lead inhibitor, 10A, was designed with the aid of X-ray crystallography and molecular modeling to bind to the allosteric AMP binding site of FBPase. High potency (IC50 = 16 nM) and FBPase specificity were achieved by linking a 2-aminothiazole with a phosphonic acid. Free-energy perturbation calculations provided insight into the factors that contributed to the high binding affinity. 10A and standard phosphonate prodrugs of 10A exhibited poor oral bioavailability (0.2-11%). Improved oral bioavailability (22-47%) was achieved using phosphonate diamides that convert to the corresponding phosphonic acid by sequential action of an esterase and a phosphoramidase. Oral administration of the lead prodrug, MB06322 (30, CS-917), to Zucker Diabetic Fatty rats led to dose-dependent inhibition of gluconeogenesis and endogenous glucose production and consequently to significant blood glucose reduction.
Enhanced radiation late effects and cellular radiation sensitivity in an ATM heterozygous breast cancer patient (1999)

We observed severe late effects in a patient treated with radiation therapy for breast cancer. Radiation survival studies of patient fibroblasts show an enhanced cellular radiation sensitivity (Do = 0.95 Gy). Genetic analysis reveals that the patient is heterozygous for a mutated ATM gene. Protein truncation test (PTT) and sequence analysis identified a truncation within the leucine zipper domain, corresponding to a fragment previously reported to exhibit dominant negative function. These findings demonstrate that ATM heterozygosity may be associated with enhanced clinical radiation sensitivity and suggest a clinical relevance to this truncation that results in a dominant negative-acting protein.
Abstract 4007: A novel immunotherapy, INT230-6, is able to induce high rates of complete response in mice through a cytotoxic T-cell-dependent mechanism (2016)

Abstract INT-230-6 is a combination of cisplatin, vinblastine and an amphiphilic cell penetration excipient that when administered intratumorally (IT) can induce complete regression in drug-injected and bystander established colon26 tumors. INT230-6 also has the ability to induce long term protection in mice against intravenous (IV) or subcutaneous (SC) re-inoculation of the cancer cells. This long term protection is dependent on induction of both CD4 and CD8 cells as evidenced by in vivo depletion prior to tumor re-inoculation. Previous studies had not elucidated whether the initial drug-injected tumor regression in naive mice was mainly due to the formulation's direct cytotoxicity or whether early tumor regression is dependent also on immune- based cell killing. To address this question, BALB/c mice were inoculated with 1×106 Colon26 cells SC. Tumors were grown to a mean of 300mm3. INT230-6 was administered intratumorally daily for 5 days (day 0 to 4). At the same time mice were treated either with an IgG control, or with rat anti mouse anti-CD4, anti-CD8 or both anti -CD4/CD8 on days 0,1,5,8,15. T cell subset depletion was confirmed by flow cytometry. In preliminary data, INT230-6 treatment resulted in regression from baseline in all mice with a complete regression of the large tumors in 40-80% of mice in the INT230-6 arm alone or the arm with IgG control. The CD4 depleted mice had a similar CR rate of 70%. However, in the CD8 depleted or the dual depleted (CD4/8) mice, tumors regrew after initial regression and no CR was observed. These results suggest that intratumoral administration of INT230-6 in addition to improving the direct cytotoxicity of cisplatin and vinblastine (data shown previously), also induces a potent CD8 tumor-specific T-cell response which participates in regression of the injected lesion, and may be able to similarly target distant lesions such as metastases. Citation Format: Ian B. Walters, Anja C. Bloom, Lewis H. Bender, Masaki Terabe, Jay A. Berzofsky. A novel immunotherapy, INT230-6, is able to induce high rates of complete response in mice through a cytotoxic T-cell-dependent mechanism. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4007.
Self-Propagating High-Temperature Synthesis Reactions for ISRU and ISFR Applications (2011)

In the framework of ISRU (In-Situ Resource Utilization) and ISFR (In-Situ Fabrication and Repair) applications, a novel recently patented process based on the occurrence of Self-propagating High temperature Synthesis (SHS) reactions potentially exploitable for the in-situ fabrication of construction materials in Lunar and Martian environments is described in this work. Specifically, the SHS process involves thermite reactions type between Lunar or Martian regolith simulants and aluminum as reducing agent. To overcome the fact that the original content of ilmenite (FeTiO3) and ferric oxide (Fe2O3) on Moon and Mars soils, respectively, is not enough to make the SHS process possible, suitable amounts of these species have to be added to the starting mixtures. The dependence of the most important processing parameters, particularly the composition of thestarting mixture, evacuation level, and gravity conditions, on SHS process behaviour and product characteristics is specifically examined for the case of Lunar regolith. All the obtained findings allows usto conclude that the optimized results obtained under terrestrial conditions are valid for in-situ applications in Lunar environment. In particular, parabolic flight experiments evidenced that neither SHS process dynamics nor product characteristics are significantly influenced in both Lunar and Martian systems when passing from Earth to low gravity conditions. Finally, the complete scheme involving all stages required for the fabrication of physical assets to be used as protection against solar rays, solar wind and meteoroids, etc., is reported.
Measurements of Relative Displacement and Tilting of a Piston Rod Transmission in a Submerged Linear Wave Energy Converter Operating with End Stop Impact (2012)

A type of piston rod mechanical-lead through transmission has been designed and implemented inside the two first wave energy converter (WEC) prototypes at the Lysekil wave energy research site on t ...
The acoustics progeny of R. Bruce Lindsay (2007)

R. Bruce Lindsay served on the faculties of Yale University from 1923 to 1930, and Brown University from 1931 until his death in 1985, a total of sixty-two years. Over that time he produced at least thirty-five Ph.D. students and a like number of masters students. Many of these students were active in acoustics, held faculty positions, and went on to produce Ph.D. students of their own. This paper attempts to trace the major branches of the acoustics family tree of R. Bruce Lindsay, which is now in at least its fifth generation. The members of the Lindsay family tree have made, and continue to make, significant contributions to acoustics. For example, it is interesting to note that James Finneran, the 2002 winner of the ASAs R. Bruce Lindsay Award, is R. Bruce Lindsays academic great-great grandchild.
BCL6 gene translocation in follicular lymphoma: a harbinger of eventual transformation to diffuse aggressive lymphoma (2003)

Follicular lymphoma (FL) is characterized by a relatively indolent clinical course, but the disease often transforms into a more aggressive large cell lymphoma with a rapidly progressive clinical course. In the present study, we analyzed 41 cases of FL known to have subsequently transformed to aggressive lymphoma and an additional 64 FL samples from patients not subsequently transformed. We studied BCL6 gene rearrangement by the methodology of long-distance inverse polymerase chain reaction (LDI-PCR). Of the 41 cases known to transform, 16 (39.0%) harbored BCL6 translocation or deletion at the time of FL diagnosis. Among 64 cases not known to transform, BCL6 translocation was detected in 9 (14.1%). The prevalence of BCL6 translocation in the group known to transform was significantly higher (P =.0048). Among the transformation cases, the partners of the BCL6 translocation were identified in 13 cases and included IGH, CIITA, U50HG, MBNL, GRHPR, LRMP, EIF4A2, RhoH/TTF, and LOC92656 (similar to NAPA), whereas in the control group the BCL6 partners were IGH, CIITA, SIAT1, and MBNL. In 13 cases paired specimens before and after transformation were available. Among these paired specimens, a loss (3 cases) or a gain (1 case) of BCL6 translocation was observed after the transformation. Analysis of clonality showed that all of these cases represented the evolution of a subclone of the original tumor population. Our study demonstrated that BCL6 translocation is not necessary for transformation but that BCL6 translocation in FL may constitute a subgroup with a higher risk to transform into aggressive lymphoma.
Cancer stem cells from peritumoral tissue of glioblastoma multiforme: the possible missing link between tumor development and progression (2018)

In glioblastoma multiforme (GBM), cancer stem cells (CSCs) are thought to be responsible for gliomagenesis, resistance to treatment and recurrence. Unfortunately, the prognosis for GBM remains poor and recurrence frequently occurs in the peritumoral tissue within 2 cm from the tumor edge. In this area, a population of CSCs has been demonstrated which may recapitulate the tumor after surgical resection. In the present study, we aimed to characterize CSCs derived from both peritumoral tissue (PCSCs) and GBM (GCSCs) in order to deepen their significance in GBM development and progression. The stemness of PCSC/GCSC pairs obtained from four human GBM surgical specimens was investigated by comparing the expression of specific stem cell markers such as Nestin, Musashi-1 and SOX2. In addition, the growth rate, the ultrastructural features and the expression of other molecules such as c-Met, pMet and MAP kinases, involved in cell migration/invasion, maintenance of tumor stemness and/or resistance to treatments were evaluated. Since it has been recently demonstrated the involvement of the long non-coding RNAs (lncRNAs) in the progression of gliomas, the expression of H19 lncRNA, as well as of one of its two mature products miR-675-5p was evaluated in neurospheres. Our results show significant differences between GCSCs and PCSCs in terms of proliferation, ultrastructural peculiarities and, at a lower extent, stemness profile. These differences might be important in view of their potential role as a therapeutic target.
Supplemental Figure 2 from Generation 2.5 Antisense Oligonucleotides Targeting the Androgen Receptor and Its Splice Variants Suppress Enzalutamide-Resistant Prostate Cancer Cell Growth (2023)

&lt;p&gt;Supplemental Figure 2. AR and mutation F876S status in ENZ-R LNCaP cells and xenografts.&lt;/p&gt;
BOTH MECHANICAL AND PHARMACOLOGICAL PRECONDITIONING DECREASE HEPATIC LEUKOCYTE/ENDOTHELIAL CELL INTERACTIONS (1999)

426 Introduction-Ischemic preconditioning(IPC) has been shown to protect some tissues from ischemia/reperfusion (I/R) injury. Adenosine is believed to play an important role by attenuating leukocyte-endothelial cell adhesive interactions. Dipyridamole increases adenosine bioavailability. The purpose of this study was to evaluate the effects of mechanical and pharmacological preconditioning on leukocyte endothelial cell interaction in hepatic I/R injury. Methods-C57BL6 mice were subjected to 30 minutes of ischemia to the left lobe of the liver. Groups tested at 30 min, 2, 5, 12, and 24 hours of reperfusion were 1.) sham laparotomy (n=10) 2.) I/R (n=25) 3.) mechanical preconditioning (MPC) with 5 min ischemia and 10 min reperfusion prior to I/R (n=25) and 4.) pharmacological preconditioning (PPC) with dipyridamole (n=25). Intravital microscopy was used to assess leukocyte/endothelial cell adhesion. Blood was drawn for leukocyte counts and liver function tests. Results-A significant decreases in leukocyte rolling was observed in all time intervals in the PPC and MPC groups (except PPC at 2hrs) compared with the I/R group. A significant decrease in leukocyte saltation was also observed in the PPC and MPC groups in all time intervals except 24hrs when compared with the I/R group. (Figure)FigureAST was significantly decreased in the 5 hr preconditioning groups. There was not a significant decrease in the WBC count due to PPC or MPC vs. I/R. Conclusions-Preconditioning decreases endothelial/leukocyte interaction and reduces liver damage as measured by AST. This data proves that mechanical and pharmacological preconditioning provide some degree of hepatic protection in ischemia reperfusion injury.
Measured Delay and Doppler Profiles of Overtaking Vehicles at 60 GHz (2018)

We report results from real-world millimetre wave vehicle-to-vehicle channel measurements carried out in an urban street environment, down-town Vienna, Austria. Channel measurements have been acquired with a time-domain channel sounder in the frequency band 59.75-60.25 GHz with a frequency resolution of approximately 5 MHz. We estimate the local scattering function for sequential stationarity regions in time. A multitaper estimator is used to precisely define Doppler and delay resolutions. Estimates for delay and Doppler profiles are evaluated from the local scattering function for several overtaking vehicles at a variety of speeds and for different types of vehicles. The results show that passenger cars are associated with a single Doppler trajectory, whereas larger vehicles, such as trucks, show up in the data with multiple Doppler trajectories.
Microfluidic devices for studies of shear-dependent platelet adhesion (2008)

Adhesion of platelets to blood vessel walls is a shear stress dependent process that promotes arrest of bleeding and is mediated by the interaction of receptors expressed on platelets with various extracellular matrix (ECM) proteins that may become exposed upon vascular injury. Studies of dynamic platelet adhesion to ECM-coated substrates in conventional flow chambers require substantial fluid volumes and are difficult to perform with blood samples from a single laboratory mouse. Here we report dynamic platelet adhesion assays in two new microfluidic devices made of PDMS. Small cross-sections of the flow chambers in the devices reduce the blood volume requirements to <100 microl per assay, making the assays compatible with samples of whole blood obtained from a single mouse. One device has an array of 8 flow chambers with shear stress varying by a factor of 1.93 between adjacent chambers, covering a 100-fold range from low venous to arterial. The other device allows simultaneous high-resolution fluorescence imaging of dynamic adhesion of platelets from two different blood samples. Adhesion of platelets in the devices to three common ECM substrate coatings was verified to conform with published results. The devices were subsequently used to study the roles of extracellular and intracellular domains of integrin alphaIIbbeta3, a platelet receptor that is a central mediator of platelet aggregation and thrombus formation. The study involved wild-type mice and two genetically modified mouse strains and showed that the absence of the integrin impaired adhesion at all shear stresses, whereas a mutation in its intracellular domain reduced the adhesion only at moderate and high stresses. Because of small sample volumes required, the devices could be employed in research with genetically-modified model organisms and for adhesion tests in clinical settings with blood from neonates.
Unstable Thoracolumbar and Lumbar Burst Fractures Treated with the AO Fixateur Interne (1992)

Benson, D. R.; Burkus, J. K.; Montesano, P. X.; Sutherland, T.; McLain, R. Author Information
Determination of sample temperature in unstable static fields by combining solid-state 79Br and 13C NMR (2014)

Monitoring the isotropic chemical shifts to calibrate the sample temperature presupposes a perfect stability of the static magnetic field. It can be difficult to satisfy this requirement in solid-state NMR measurements. This paper describes a simple way to recover the accurate temperature dependence of the (79)Br resonance after subtracting changes of resonance frequency due to variations of the static field, monitored by the (13)C resonance.
Error-free 850nm to 1060nm VCSEL links : feasibility of 400Gbps and 800Gbps 8λ-SWDM (2019)

We demonstrate effective transmitter equalization for 850nm, 980nm, and 1060nm VCSELs and 100m OM5 links enabling 78Gbps PAM-2 and >100Gbps PAM-4 100m error free links. Extracted link penalties reveal net fibre dispersion and RIN enhancement create small to negligible power penalties for all wavelengths.