gebhart/patrepeval huggingface dataset:
RETINAL VASCULAR OCCLUSIONS AND MACULAR THINNING IN FIBROMUSCULAR DYSPLASIA (2010)

In Brief Purpose: To report retinal findings in a patient with fibromuscular dysplasia. Methods: A retrospective case report. Results: A 36-year-old female patient with fibromuscular dysplasia and a history of cerebrovascular events presented with painless vision loss in the left eye. Ophthalmologic evaluation demonstrated retinal vascular occlusive disease and secondary macular thinning. Conclusion: This case demonstrates that fibromuscular dysplasia can affect the retinal vasculature and lead to macular ischemia and vision loss. A case of fibromuscular dysplasia with associated retinal vascular occlusive disease and macular atrophy is reported.
Comprehensive profiling of cancer associated cells in the blood of breast cancer patients to predict pathological complete response. (2022)

e12603 Background: Goal of neoadjuvant chemotherapy (NAC) has expanded from increasing the rate of breast conservation to in vivo assessment of response for use of second line therapies that increase survival. Pathological complete response (pCR) is a desirable goal of NAC; however, prediction of pCR for individualized therapeutic decisions remains a vexing problem. Cancer associated cells in the blood provide a promising venue to research response to therapy. Circulating tumor cells (CTCs) are of epithelial origin [CTCs (E+)] that undergo epithelial to mesenchymal transition [CTCs (E+M+)] to become motile and invasive; leading to fully invasive mesenchymal [CTCs (M+)] cells that seed in distant organs, causing metastasis. In addition, cancer associated macrophage-like cells (CAMLs) in the blood of cancer patients are reported to either engulf or aid the transport of cancer cells to distant organs. A comprehensive evaluation of these cancer associated circulating cells through liquid biopsy has a potential to provide a much needed biomarker to predict pCR. Methods: Patients treated with NAC with an intention to cure were enrolled in the study. Blood was collected at 3 time points: pre, mid and post NAC. Microfluidics-based label-free Labyrinth technology was used to isolate CTCs and CAMLs from the blood. Data was collected for patient demographics, biological tumor markers, and treatment response from medical records including pathology reports. Residual Cancer Burden Index (RCBI) and class (pCR vs. residual disease) were analyzed as dependent variables. Independent variables included CTCs, CAMLs and tumor receptor status for univariate and multivariate models to assess the combined effects using R. Results: A total of 57 samples from 19 patients were analyzed. Univariate regression models predicting RCBI or pCR using CTCs and CAML did not show any significant associations. However, in multivariate regression analysis predicting RCBI, an increase in post-NAC CAML and a decrease in post-NAC CTCs were associated with a decrease in RCBI (p=0.005, p=0.035, respectively). In a multivariate logistic regression model predicting pCR, CAML was positively associated with the log-odds of pCR (OR=1.60 [1.01, 2.54]; p=0.047), while CTCs showed a trend in negatively predicting pCR (OR=0.33 [0.10, 1.06]; p=0.063). When controlled for each other, increased CAML and decreased CTCs were associated with increased pCR. While increased M+ was associated with the decreasing log-odds of pCR (OR=0.27 [0.08, 0.99]; p=0.049), neither E+ nor E+M+ was associated with pCR. Conclusions: Increased CAMLs in circulation after treatment combined with lowered CTCs are associated with pCR and lower RCBI. M+ cells could be a factor governing association between CTCs and pCR.
Supplementary Table 4 from Targeting the PI3K Pathway in the Brain—Efficacy of a PI3K Inhibitor Optimized to Cross the Blood–Brain Barrier (2023)

&lt;p&gt;PDF file - 47K, Anti-proliferative EC50's for GNE-317 against a Panel of Nine Glioma Cell lines&lt;/p&gt;
Single Nanocrystal Arrays on Patterned Poly(ethylene glycol) Copolymer Microstructures Using Selective Wetting and Drying (2004)

Single nanocrystal arrays were fabricated on sub-microwells of poly(ethylene glycol) (PEG) copolymer using selective wetting on the hydrophilic regions of the exposed substrate surface and subsequent drying. Templates were produced by molding a thin film of a PEG-based random copolymer on hydrophilic substrates such as glass or silicon dioxide. The polymeric microstructures provide a topographical barrier around the well, which makes it possible to create nanocrystal arrays with controlled geometrical features. The size of the nanocrystal was found to decrease with decreasing well size and also decrease with decreasing topological height. A simple empirical equation was derived to predict the size of the crystal as a function of the pattern size and height, which is in good agreement with the experimental data.
Heparan sulfate differences in rheumatoid arthritis versus healthy sera (2014)

Heparan sulfate (HS) is a complex and highly variable polysaccharide, expressed ubiquitously on the cell surface as HS proteoglycans (HSPGs), and found in the extracellular matrix as free HS fragments. Its heterogeneity due to various acetylation and sulfation patterns endows a multitude of functions. In animal tissues, HS interacts with a wide range of proteins to mediate numerous biological activities; given its multiple roles in inflammation processes, characterization of HS in human serum has significant potential for elucidating disease mechanisms. Historically, investigation of HS was limited by its low concentration in human serum, together with the complexity of the serum matrix. In this study, we used a modified mass spectrometry method to examine HS disaccharide profiles in the serum of 50 women with rheumatoid arthritis (RA), and compared our results to 51 sera from healthy women. Using various purification methods and online LC-MS/MS, we discovered statistically significant differences in the sulfation and acetylation patterns between populations. Since early diagnosis of RA is considered important in decelerating the disease's progression, identification of specific biomolecule characterizations may provide crucial information towards developing new therapies for suppressing the disease in its early stages. This is the first report of potential glycosaminoglycan biomarkers for RA found in human sera, while acknowledging the obvious fact that a larger population set, and more stringent collection parameters, will need to be investigated in the future.
Feasibility of Using Electrocochleography for Objective Estimation of Electro-Acoustic Interactions in Cochlear Implant Recipients with Residual Hearing (2017)

Although cochlear implants (CI) traditionally have been used to treat individuals with bilateral profound sensorineural hearing loss, a recent trend is to implant individuals with residual low-frequency hearing. Patients who retain some residual acoustic hearing after surgery often can benefit from electro-acoustic stimulation (EAS) technologies, which combine conventional acoustic amplification with electrical stimulation. However, interactions between acoustic and electrical stimulation may affect outcomes adversely and are time-consuming and difficult to assess behaviorally. This study demonstrated the feasibility of using the Advanced Bionics HiRes90K Advantage implant electronics and HiFocus Mid Scala/1j electrode to measure electrocochleography (ECochG) responses in the presence of electrical stimulation to provide an objective estimate of peripheral physiologic EAS interactions. In general, electrical stimulation reduced ECochG response amplitudes to acoustic stimulation. The degree of peripheral EAS interaction varied as a function of acoustic pure tone frequency and the intra-cochlear location of the electrically stimulated electrode. Further development of this technique may serve to guide and optimize clinical EAS system fittings in the future.
Separable fluorous ionic liquids for the dissolution and saccharification of cellulose (2011)

Ionic liquids are an attractive class of solvents for biomass conversion processes. The same properties that make them advantageous—high polarity, water solubility and negligible vapor pressure—hinder their recovery from carbohydrates. We report on the synthesis of seven fluorous imidazolium chloride ionic liquids and on their ability to dissolve cellulose. One of these ionic liquids, 3-methyl-1-(2′,2′,3′,3′,3′-pentafluoropropyl)-imidazolium chloride, dissolves cellulose. We found this fluorous ionic liquid to be suitable for use in cellulose hydrolysis reactions, and we achieved its recovery from glucose.
Identification of Phosphorylation Sites of TOPORS and a Role for Serine 98 in the Regulation of Ubiquitin but Not SUMO E3 Ligase Activity (2008)

TOPORS is the first example of a protein that possesses both ubiquitin and SUMO E3 ligase activity. The ubiquitination activity maps to a conserved RING domain in the N-terminal region of the protein, which is not required for sumoylation activity. Similar to other E3 ligases, it is likely that the ubiquitin and sumoylation activities of TOPORS are regulated by post-translational modifications. Therefore, we employed mass spectrometry to identify post-translational modifications of TOPORS. Several putative phosphorylated regions were identified in conserved regions of the protein. We investigated the role of phosphorylation of serine 98, which is adjacent to the RING domain, in both cells and in vitro. Mutation of serine 98 to aspartic acid resulted in an increase in the ubiquitin ligase activity of TOPORS both in cells and in vitro. In addition, this mutation increased the binding of TOPORS to the E2 enzyme UbcH5a both in vitro and in cells. Conversely, a phospho-deficient mutant (S98A) exhibited little change in ubiquitin ligase activity compared to wild-type TOPORS, both in cells and in vitro. Neither of the mutants affected the localization of TOPORS to punctate nuclear regions. In addition, neither mutant affected the SUMO ligase activity of TOPORS in cells or in vitro. Molecular modeling studies support a role for serine 98 in regulating TOPORS-E2 interactions. Our findings indicate that phosphorylation of serine 98 regulates the ubiquitin but not the SUMO ligase activity of TOPORS, consistent with a potential binary switch function for TOPORS in protein ubiquitination versus sumoylation.
Long-Lasting Desynchronization of Plastic Neuronal Networks by Double-Random Coordinated Reset Stimulation (2022)

Hypersynchrony of neuronal activity is associated with several neurological disorders, including essential tremor and Parkinson's disease (PD). Chronic high-frequency deep brain stimulation (HF DBS) is the standard of care for medically refractory PD. Symptoms may effectively be suppressed by HF DBS, but return shortly after cessation of stimulation. Coordinated reset (CR) stimulation is a theory-based stimulation technique that was designed to specifically counteract neuronal synchrony by desynchronization. During CR, phase-shifted stimuli are delivered to multiple neuronal subpopulations. Computational studies on CR stimulation of plastic neuronal networks revealed long-lasting desynchronization effects obtained by down-regulating abnormal synaptic connectivity. This way, networks are moved into attractors of stable desynchronized states such that stimulation-induced desynchronization persists after cessation of stimulation. Preclinical and clinical studies confirmed corresponding long-lasting therapeutic and desynchronizing effects in PD. As PD symptoms are associated with different pathological synchronous rhythms, stimulation-induced long-lasting desynchronization effects should favorably be robust to variations of the stimulation frequency. Recent computational studies suggested that this robustness can be improved by randomizing the timings of stimulus deliveries. We study the long-lasting effects of CR stimulation with randomized stimulus amplitudes and/or randomized stimulus timing in networks of leaky integrate-and-fire (LIF) neurons with spike-timing-dependent plasticity. Performing computer simulations and analytical calculations, we study long-lasting desynchronization effects of CR with and without randomization of stimulus amplitudes alone, randomization of stimulus times alone as well as the combination of both. Varying the CR stimulation frequency (with respect to the frequency of abnormal target rhythm) and the number of separately stimulated neuronal subpopulations, we reveal parameter regions and related mechanisms where the two qualitatively different randomization mechanisms improve the robustness of long-lasting desynchronization effects of CR. In particular, for clinically relevant parameter ranges double-random CR stimulation, i.e., CR stimulation with the specific combination of stimulus amplitude randomization and stimulus time randomization, may outperform regular CR stimulation with respect to long-lasting desynchronization. In addition, our results provide the first evidence that an effective reduction of the overall stimulation current by stimulus amplitude randomization may improve the frequency robustness of long-lasting therapeutic effects of brain stimulation.
Internet Scale Testing of PNRP Using WiDS Network Simulator (2006)

PNRP (peer name resolution protocol) is a decentralized name resolution and routing protocol built into the Windowstrade operating system that creates an Internet-scale peer-to-peer structured overlay. Ensuring the protocol's performance in Internet scale presents a critical challenge. We describe Internet scale testing of PNRP using a distributed network simulator, WiDS. We use real-world Internet characteristics and PNRP node behaviors to simulate the Internet environment, assess PNRP performance, and support protocol debugging. A case study demonstrates identification of a protocol flaw that could otherwise only be discovered through full-scale deployment experience
Homeodomain-interacting protein kinase 2-dependent repression of myogenic differentiation is relieved by its caspase-mediated cleavage (2013)

Differentiation of skeletal muscle cells is accompanied by drastic changes in gene expression programs that depend on activation and repression of genes at defined time points. Here we identify the serine/threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) as a corepressor that inhibits myocyte enhancer factor 2 (MEF2)-dependent gene expression in undifferentiated myoblasts. Downregulation of HIPK2 expression by shRNAs results in elevated expression of muscle-specific genes, whereas overexpression of the kinase dampens transcription of these genes. HIPK2 is constitutively associated with a multi-protein complex containing histone deacetylase (HDAC)3 and HDAC4 that serves to silence MEF2C-dependent transcription in undifferentiated myoblasts. HIPK2 interferes with gene expression on phosphorylation and HDAC3-dependent deacetylation of MEF2C. Ongoing muscle differentiation is accompanied by elevated caspase activity, which results in caspase-mediated cleavage of HIPK2 following aspartic acids 916 and 977 and the generation of a C-terminally truncated HIPK2 protein. The short form of the kinase loses its affinity to the repressive multi-protein complex and its ability to bind HDAC3 and HDAC4, thus alleviating its repressive function for expression of muscle genes. This study identifies HIPK2 as a further protein that determines the threshold and kinetics of gene expression in proliferating myoblasts and during the initial steps of myogenesis.
Optical memory using a vertical-cavity surface emitting laser (1991)

Data are presented demonstrating optical switching and memory in a bistable vertical-cavity surface-emitting laser (VCSEL). Optical switching from lasing to nonlasing or from nonlasing to lasing in the vertical-cavity laser was demonstrated using an AlGaAs probe laser at approximately 0.78 mu m.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
SU‐GG‐T‐408: Validation of a Novel Dose Calculation Approach for Heterogeneous Voxelized Phantoms in a Parallel Computation Environment Using Electron Dose Kernels for Radiotherapy (2010)

Purpose Here we present a rapid whole body dose estimation approach applied to a clinical water phantom and whole body CT‐voxelized phantom, using electron dose kernels coupled with deterministic photon transport. This method yields fast, accurate whole body doses. Method and Materials A novel dose calculation methodology called EDK‐S N , or “Electron Dose Kernel‐Discrete Ordinates” rapidly estimates organ doses in a voxelized human phantom, accounts for in‐ and out‐of‐field doses using external photon beam therapy. We begin by solving the complete photon transport problem using parallel computing with the 3‐D discrete ordinates (S N ) photon transport code PENTRAN. We then project pre‐computed (via Monte Carlo) voxel‐based Electron Dose Kernels (EDKs), mapping them to surrounding voxels via quaternion rotation, scaled by the magnitude of photon fluence from the S N calculation. An 8 MV flat‐weighted beam is incident on an 11×11×11 cm 3 water phantom, and on a 15 year old human phantom, down‐sampled to 1×1×1 cm 3 (60×27×167 voxels); a 6 MV Philips Elekta Linac photon spectrum has also been simulated. The percent depth dose was compared to clinical CC04 chamber measurement results; comparison of doses using the EDK‐Sn method and clinical treatment planning system (in field dose) will also be presented. Results The EDK‐S N technique has demonstrated independent agreement with Monte Carlo photon‐electron transport calculations for whole body dose. The EDK‐S N method yields a speedup of ∼8 (30 minutes versus 4+ hours) over the traditional parallel Monte Carlo, with &lt;7% difference in different organs (smaller given stochastic uncertainties). The Monte Carlo simulated percent depth dose and clinical chamber PDD measurement agree within 10% among different field sizes. Conclusion The EDK‐S N method for high energy photon external beam dose calculations has been validated based on clinical external therapy beam calculations. This method will help to determine both in‐field and out‐of‐field radiation dose for radiotherapy.
Supplementary Figure 5 from MYC-Driven Tumorigenesis Is Inhibited by WRN Syndrome Gene Deficiency (2023)

&lt;p&gt;PDF file - 101K&lt;/p&gt;
Anti‐KIT monoclonal antibody CDX‐0159 induces profound and durable mast cell suppression in a healthy volunteer study (2022)

CDX-0159 administration leads to systemic mast cell ablation and may represent a safe and novel approach to treat mast cell-driven disorders.
Successful Expansion of Umbilical Cord Blood Cells as a Source of Hematopoietic Progenitors for Adult Transplantation. (2004)

Abstract The low yield of progenitor CD34+ cells recovered from umbilical cord blood (UCB) limits the utility of this source for transplantation in adults. This limitation has triggered investigations into how ex vivo expansion of hematopoietic stem cells (HSC) could be achieved to allow for transplantation in larger recipients. In the present study, the incubation of MNC and not selected CD34+cells in the presence of SCF 25ng/ml+MGDF 10ng/ml+FLt-3 25ng/ml+IL-6 20ng/ml, and 10% human serum in stroma-free liquid culture generated long-term expansion of transplantable UCB HSC. In vitro, HSC expansion from 13 UCB lasted &amp;gt;7 months giving 39, 1.3x104, and 4.7 x109 fold increase in total cell count after 14, 70 and 217 d of expansion as compared to d0 (105/ml). Similarly, CD34+ and CD34+/CD38− cell populations increased reaching 229 and 2.2x105 and 91 and 2.2x104 fold after 14 and 70d of expansion. Examination of cell morphology and analysis by flow cytometry showed the presence of primitive and mature cells belonging to all hematopoietic cell lineages. Similarly, multilineage colonies with recloning capacity were generated in culture. Erythroid, myeloid and mixed colonies increased by 116 and 1.8x104 fold and megakaryocytic colonies by 8 and 527 fold after 14 and 70d. Expanded cells were karyotypically normal and lacked the most common chromosome translocations seen in AML and CML t (15,17) and t (9, 22). HSC expanded for 6 and 13 weeks and cropreserved for 6–11 months were able to re-expand in liquid culture and generate colonies capable of recloning and multi-lineage differentiation. We estimated the frequency of SCID repopulating cells (SRC) in UCB samples expanded for 2 and 12 w using 1000,500,250 and 125 unselected CD34+ cells injected intravenously into sublethally irradiated NOD/SCID mice. Mice were sacrificed 20 weeks after transplantation. Human cell engraftment measured as CD45+ (HuCD45+) was detected in all mice (x3mice/dilution) (0.1–9.8%). In addition, HuCD45+ cells with multilineage phenotype were present, (CD19 (lymphoid), CD33 (myeloid), CD71and Glycophorin-A (erythroid) as well as CD34+/CD38− cells). SRC increased by 90 fold after 2 weeks of expansion and by 187 fold after 12 weeks compared to unexpanded CD34+cells. Additional proof of human cell engraftment was documented using semisolid culture (MethoCultTM GF H4434 Stem Cell Technologies). Human myeloid and erythroid colonies were generated from all dilutions, and counts ranged between 63–271/500,000 MNC. Initial studies to test the relative magnitude of UCB HSC expansion from 24-well plates to culture bags (OptiCyte TM, Baxter) using one UCB, the total cell count increased by (6.3 and 20 (bags) Vs 2.3 and 3.3 fold (wells) after 7 and 14d) and CD34+ subpopulations including CD34+/CD38−. Based on these ongoing results, a phase II clinical trial using ex vivo expanded UCB for 14d in a setting of sub ablative Conditioning is planned.
An automated image processing method to quantify collagen fibre organization within cutaneous scar tissue (2014)

Standard approaches to evaluate scar formation within histological sections rely on qualitative evaluations and scoring, which limits our understanding of the remodelling process. We have recently developed an image analysis technique for the rapid quantification of fibre alignment at each pixel location. The goal of this study was to evaluate its application for quantitatively mapping scar formation in histological sections of cutaneous burns. To this end, we utilized directional statistics to define maps of fibre density and directional variance from Masson's trichrome-stained sections for quantifying changes in collagen organization during scar remodelling. Significant increases in collagen fibre density are detectable soon after burn injury in a rat model. Decreased fibre directional variance in the scar was also detectable between 3 weeks and 6 months after injury, indicating increasing fibre alignment. This automated analysis of fibre organization can provide objective surrogate endpoints for evaluating cutaneous wound repair and regeneration.
An integrated recirculating optical buffer (2008)

This paper reports an integrated optical buffer consisting of a low loss silicon waveguide delay line and a silicon evanescent gate matrix switch. The integrated device demonstrates an error free operation at 40 Gb/s data rate with a packet delay of 1.1 ns. This demonstration also highlights the silicon evanescent device platform to realize new types of photonic integrated devices by combining the low loss silicon passive components with the silicon evanescent photonic active devices.