gebhart/patrepeval huggingface dataset:
Pharmacological chaperones increase the cell-surface expression of intracellularly retained mutants of the melanocortin 4 receptor with unique rescuing efficacy profiles (2012)

Mutated versions of membrane proteins often fail to express at the plasma membrane, but instead are trapped in the secretory pathway, resulting in disease. The retention of these mutant proteins is thought to result from local misfolding, which prevents export from the ER (endoplasmic reticulum), targeting the receptor for degradation via the ER-associated quality control system. The rhodopsin-like G-protein-coupled MC4R (melanocortin 4 receptor) is an example of such a membrane protein. Over 100 natural MC4R mutations are linked with an obese phenotype and to date represent the most common monogenic cause of severe early-onset obesity. More than 80% of these mutations result in a substantial proportion of MC4R being retained intracellularly. If these receptors were expressed at the plasma membrane, many could be functional, as mutations often occur in regions distinct from those associated with ligand or G-protein binding. Our aim is to show proof of concept that selective compounds can rescue the function of MC4R mutants by increasing their cell-surface expression, and further to this, examine whether the rescue profile differs between mutants. Whole-cell ELISA and 96-well fluorescence-based assays with N-terminally HA (haemagglutinin)-tagged and C-terminally mCherry-tagged mutant MC4Rs were used to screen a number of novel MC4R-selective compounds. A total of four related compounds increased the cell-surface expression of wild-type and three intracellularly retained mutant MC4Rs, thus acting as pharmacological chaperones. There appears to be a unique rescue efficacy profile for each compound that does not correlate with potency, suggesting distinct receptor conformations induced by the different mutations. A degree of functionality of V50M and S58C was also rescued following relocation to the cell surface.
CoreView: Fresh Tissue Biopsy Assessment at the Bedside Using a Millifluidic Imaging Chip (2021)

Minimally invasive core needle biopsies for medical diagnoses have become increasingly common for many diseases. Although tissue cores can yield more diagnostic information than fine needle biopsies and cytologic evaluation, there is no rapid evaluation at the point-of-care for intact tissue cores that is low-cost and non-destructive to the biopsy. We have developed a proof-of-concept 3D printed millifluidic histopathology lab-on-a-chip device to automatically handle, process, and image fresh core needle biopsies. This device, named CoreView, includes modules for biopsy removal from the acquisition tool, transport, staining and rinsing, imaging, segmentation, and multiplexed storage. Reliable removal from side-cutting needles and bidirectional fluid transport of core needle biopsies from five tissue types has been demonstrated with 0.5-mm positioning accuracy. Automation is aided by a MATLAB-based biopsy tracking algorithm that can detect the location of tissue and air bubbles in the channels of the millifluidic chip. With current and emerging optical imaging technologies, CoreView can be used for a rapid adequacy test at the point-of-care for tissue identification and glomeruli counting from renal core needle biopsies, and has the potential to be used for breast cancer diagnosis, phenotyping, and mapping of enriched tumorous regions for downstream analyses in global health applications.
Insulin supplementation attenuates cancer-induced cardiomyopathy and slows tumor disease progression (2017)

Advanced cancer induces fundamental changes in metabolism and promotes cardiac atrophy and heart failure. We discovered systemic insulin deficiency in cachectic cancer patients. Similarly, mice with advanced B16F10 melanoma (B16F10-TM) or colon 26 carcinoma (C26-TM) displayed decreased systemic insulin associated with marked cardiac atrophy, metabolic impairment, and function. B16F10 and C26 tumors decrease systemic insulin via high glucose consumption, lowering pancreatic insulin production and producing insulin-degrading enzyme. As tumor cells consume glucose in an insulin-independent manner, they shift glucose away from cardiomyocytes. Since cardiomyocytes in both tumor models remained insulin responsive, low-dose insulin supplementation by subcutaneous implantation of insulin-releasing pellets improved cardiac glucose uptake, atrophy, and function, with no adverse side effects. In addition, by redirecting glucose to the heart in addition to other organs, the systemic insulin treatment lowered glucose usage by the tumor and thereby decreased tumor growth and volume. Insulin corrected the cancer-induced reduction in cardiac Akt activation and the subsequent overactivation of the proteasome and autophagy. Thus, cancer-induced systemic insulin depletion contributes to cardiac wasting and failure and may promote tumor growth. Low-dose insulin supplementation attenuates these processes and may be supportive in cardio-oncologic treatment concepts.
A Dual-Heat-Pump Residential Heating System for Shaping Electric Utility Load (2018)

We present a residential heating system designed specifically to provide electric utilities with a means for achieving intra-hour load shifting. The system couples two heat pumps with a large water tank, which serves as a thermal storage unit. One heat pump uses the water tank as a source and serves residential heating load. The other uses the outdoor air as a source and heats the water tank during favorable weather conditions, thereby improving the efficiency of the first. By aggregating large numbers of such systems distributed throughout its balancing area, a utility may use this resource as a means for achieving load shaping, the intra-hour shifting of generation resources from periods of peak demand to periods of low demand. This paper focuses on the potential for using such an aggregated resource as a technological solution for realizing winter peak demand reduction and overall lower energy consumption, thereby displacing the need for capital investment in peak generation plants. The results of this paper are promising, demonstrating potential savings for both the utility and residential customers.
Thein vivointeraction between flavone acetic acid and hyperthermia (1996)

The in vivo interaction between flavone acetic acid (FAA) and hyperthermia was studied in a C3H mammary carcinoma grown in the feet of female CDF1 mice and in normal foot skin. FAA was intraperitoneally injected prior to local tissue heating in restrained non-anaesthetized animals. Alone, FAA at doses of 100 mg/kg and above, inhibited tumour growth in a dose-dependent fashion. FAA also enhanced the tumour response to heat, the effect being dependent on both the time interval between the two modalities and the FAA dose, the greatest effect occurring when FAA doses of > or = 150 mg/kg preceeded heat by 3-48 h. These effects of FAA correlated with the drug's ability to decrease tumour blood perfusion measured using the RbCl extraction procedure. Injecting 150 mg/kg FAA 3 h before heating (42.7 degrees C) resulted in a 2.2-fold increase in tumour heat damage, but had little effect on the response of normal foot skin in non-tumour-bearing mice. However, this treatment gave a 2.0-fold increase in normal tissue damage when the skin experiments were repeated in tumour-bearing animals. These effects in skin occurred in the absence of any blood perfusion changes, but appeared to be associated with FAA-induced TNF-alpha production.
Integration challenges for optical inteconnects (2008)

The package integration of optical components with electronic integrated circuits (ICs) for optical interconnects is a subject of much debate and will, to a large extent, determine the performance of the optical interconnect system. In this paper we examine the challenges of incorporating optical interconnects into a computer system; specifically we cover several ways to integrate the optical components with a central processing unit (CPU) or chipset. Critical performance parameters such as the supported distance, power consumption and the achievable bandwidth are all impacted by the electrical integration between the IC and the optical components. Additional electrical link issues which also have a large impact on the performance of the link will be discussed as well; these include protocol related issues as well as signal integrity concerns, such as the jitter budget. We will also discuss the performance of some of the competing electrical technologies in order to provide a better understanding of the implementation challenge facing the developers of optical interconnect technology. Rack to rack communications are quickly moving to optical links, board to board communication is the next step and chip to chip communication is still further out as the electrical solutions for this topology have a great deal of headroom.
Leveraging kinase inhibitors to develop small molecule tools for imaging kinases by fluorescence microscopy (2012)

As the usage of fluorescence microscopy as a tool to study biological systems continues to grow, so does the need for additional tools that permit the selective detection of proteins of interest. Existing selective and well-characterized kinase inhibitors may be exploited to develop novel small molecule probes useful in imaging kinases by fluorescence microscopy.
Flavonoids synthesis. I. Synthesis and spectroscopic properties of flavones with two hydroxy and five methoxy groups at C-2',3',4',5,6,6',7 and C-2',3,4',5,5',6,7. (1986)

Four flavones oxygenated at C-2', 3', 4' and 6', and seven flavonols oxygenated at C-2', 4' and 5', each with a 5, 6, 7-trioxygenated structure in ring A, were synthesized for comparison with brickellin and apulein. The structures of brickelin and apulein were thus confirmed to be 2', 5-dihydroxy-3, 4', 5', 6, 7-pentamethoxyflavone and 2', 5'-dihydroxy-3, 4', 5, 6, 7-pentamethoxyflavone, respectively. The differences between flavones oxygenated at 2', 3', 4' and 6', and flavonols oxygenated at C-2', 4', 5' are discussed on the basis of spectroscopic data.
Multimodal MRI as a diagnostic biomarker for amyotrophic lateral sclerosis (2014)

Combining multiple advanced neuroimaging modalities significantly improves disease discrimination between ALS patients and healthy controls. These results provide an important step toward advancing a multimodal MRI approach along the diagnostic test development pathway for ALS.
Geopyxins A–E, ent-Kaurane Diterpenoids from Endolichenic Fungal Strains Geopyxis aff. majalis and Geopyxis sp. AZ0066: Structure–Activity Relationships of Geopyxins and Their Analogues (2012)

Four new ent-kaurane diterpenoids, geopyxins A–D (1–4), were isolated from Geopyxis aff. majalis, a fungus occurring in the lichen Pseudevernia intensa, whereas Geopyxis sp. AZ0066 inhabiting the same host afforded two new ent-kaurane diterpenoids, geopyxins E and F (5 and 6), together with 1 and 3. The structures of 1–6 were established on the basis of their spectroscopic data, while the absolute configurations were assigned using modified Mosher’s ester method. Methylation of 1–3, 5, and 6 gave their corresponding methyl esters 7–11. On acetylation, 1 and 7 yielded their corresponding monoacetates 12 and 14 and diacetates 13 and 15. All compounds were evaluated for their cytotoxic and heat-shock induction activities. Compounds 2, 7–10, 12, 14, and 15 showed cytotoxic activity in the low micromolar range against all five cancer cell lines tested, but only compounds 7–9, 14, and 15 were found to activate the heat-shock response at similar concentrations. From a preliminary structure–activity perspective, the electrophilic α,β-unsaturated ketone carbonyl motif present in all compounds except 6 and 11 was found to be necessary but not sufficient for both cytotoxicity and heat-shock activation.
Endoscopic management of urologic disease with the holmium laser (2000)

The efficiency and safety profile of the holmium laser have made this tool a versatile multipurpose instrument for use in the endoscopic treatment of a wide variety of urologic disorders. Herein are reviewed holmium laser physics and current endourologic applications, as well as the performance of new low-power holmium lasers.
Overexpression of the cyclin-dependent kinase inhibitor p16 is associated with tumor recurrence in human prostate cancer. (1999)

The INK4A gene maps to the 9p21 region and was initially described [M. Serrano et al., Nature (Lond.), 366: 704-707, 1993; A. Kamb et al., Science (Washington DC), 264: 436-440, 1994] as encoding a 148-amino-acid protein termed p16. The p16 protein associates exclusively with Cdk4 and Cdk6, inhibiting their complexation with D-type cyclins and the consequent phosphorylation of pRb. This contributes to cell cycle arrest. The purpose of the present study was to evaluate patterns of p16 expression in a well-characterized cohort of prostatic adenocarcinomas while exploring potential associations between alterations of p16 and clinicopathological variables. Normal and malignant tissues from 88 patients with prostate carcinoma were examined. In situ hybridization and immunohistochemistry assays were used to determine the status of the INK4A exon 1alpha transcripts and levels of p16 protein, respectively. Associations between altered patterns of expression and clinicopathological variables, including pretreatment prostate-specific antigen (PSA) level, Gleason grade, pathological stage, and hormonal status, were evaluated using the Mantel-Haenszel chi2 test. Biochemical (PSA) relapse after surgery was evaluated using the Kaplan-Meier method and the log-rank test. Levels of p16 expression and INK4A exon 1alpha transcripts in normal prostate and benign hyperplastic tissues were undetectable. However, p16 nuclear overexpression was observed in 38 (43%) prostate carcinomas, whereas the remaining 50 (57%) cases showed undetectable p16 levels. Overexpression of p16 protein was found to correlate with increased INK4A exon 1alpha transcripts. Moreover, p16 overexpression was associated with a higher pretreatment PSA level (P = 0.018), the use of neoadjuvant androgen ablation (P = 0.001), and a sooner time to PSA relapse after radical prostatectomy (P = 0.002). These data suggest that p16 overexpression is associated with tumor recurrence and a poor clinical course in patients with prostate cancer.
Modulation Depth Estimation and Variable Selection in State-Space Models for Neural Interfaces (2015)

Rapid developments in neural interface technology are making it possible to record increasingly large signal sets of neural activity. Various factors such as asymmetrical information distribution and across-channel redundancy may, however, limit the benefit of high-dimensional signal sets, and the increased computational complexity may not yield corresponding improvement in system performance. High-dimensional system models may also lead to overfitting and lack of generalizability. To address these issues, we present a generalized modulation depth measure using the state-space framework that quantifies the tuning of a neural signal channel to relevant behavioral covariates. For a dynamical system, we develop computationally efficient procedures for estimating modulation depth from multivariate data. We show that this measure can be used to rank neural signals and select an optimal channel subset for inclusion in the neural decoding algorithm. We present a scheme for choosing the optimal subset based on model order selection criteria. We apply this method to neuronal ensemble spike-rate decoding in neural interfaces, using our framework to relate motor cortical activity with intended movement kinematics. With offline analysis of intracortical motor imagery data obtained from individuals with tetraplegia using the BrainGate neural interface, we demonstrate that our variable selection scheme is useful for identifying and ranking the most information-rich neural signals. We demonstrate that our approach offers several orders of magnitude lower complexity but virtually identical decoding performance compared to greedy search and other selection schemes. Our statistical analysis shows that the modulation depth of human motor cortical single-unit signals is well characterized by the generalized Pareto distribution. Our variable selection scheme has wide applicability in problems involving multisensor signal modeling and estimation in biomedical engineering systems.
Micro-mirror On Ribbon-actuator (MOR) for high speed spatial light modulator (2008)

To realize a high throughput Optical Mask-less Lithography (OML) which is utilized for the semiconductor integrated circuit (IC) mass fabrication, we have been studying the high speed Spatial Light Modulator (SLM). In this paper, we report a Micro-mirror On Ribbon-actuator (MOR) as a novel MEMS SLM. The MOR consists of a ribbon actuator which carries a mirror placed on the offset position. The mirror tilts when the ribbon actuator is bent by electrostatic force. The high speed driving of the MOR is realized by the high resonant frequency of the ribbon actuator and the large damping factor of the submicron gap. The MOR showed the routinely switching response of less than 3 μsec and the resonant frequency of around 1.7 MHz. The 8×8 passive matrix drive of the MOR was also demonstrated.
Ovarian and Endometrial Cancer in Patients with Hereditary Non-polyposis Colorectal Cancer Syndrome (2009)

In this era of personalized medicine, genetic susceptibility to cancer is quickly becoming one of the most researched areas of the biomedical sciences. In addition, greater public understanding of the role that genes play in the development of cancer and potential testing requires that today’s physician be aware of these genetic predispositions, understand how to take a detailed family history, and be knowledgeable about the testing at his/her disposal. Hereditary non-polyposis colorectal cancer (HNPCC) is one such heritable, cancer susceptibility syndrome. The care of patients with this syndrome requires orchestrated efforts by gastroenterologists, gynecologists, surgeons, medical oncologists, and geneticists.
Scintillation-resistant wavefront sensing based on a multi-aperture phase reconstruction (MAPR) technique (2012)

A scintillation-resistant sensor that allows retrieval of an input optical wave phase using a multi-aperture phase reconstruction (MAPR) technique is introduced and analyzed. The MAPR sensor is based on a low-resolution lenslet array in the classical Shack-Hartmann arrangement and two high-resolution photo-arrays for simultaneous measurements of pupil- and focal-plane intensity distributions which are used for retrieval of wavefront phase in a two stage process: (a) phase reconstruction inside the sensor pupil sub-regions corresponding to lenslet sub-apertures, and (b) recovery of sub-aperture averaged phase components (piston phases). Numerical simulations demonstrate the efficiency of the MAPR technique in conditions of strong intensity scintillations and presence of wavefront branch points.
PAPER 013: SERUM COBALT AND CHROMIUM CONCENTRATIONS IN BILATERAL VERSUS UNILATERAL HIP RESURFACING (2010)

Purpose: Metal-on-metal (MOM) bearing surfaces release ions locally and into the systemic circulation. This elevation raises concern about the long term effects of elevated metal ions. The goal of the present study was to monitor serum cobalt (Co) and chromium (Cr) levels in patients after MOM resurfacing hip arthroplasty with the Cormet 2000 prosthesis. We present here pilot data on Co and Cr levels in patients with bilateral versus unilateral hip resurfacing devices. Method: We prospectively collected patient characteristics, outcome, and serum samples from device implanted subjects at 6 months, 1, 2, and 3 years following surgery. Unilateral patients had one implant during the entire course of follow-up and bilateral patients were included after the second implant surgery was performed. Serum Co/Cr levels were determined using high-resolution inductively coupled plasma mass spectrometry. Students t-test was used to compare ion levels in two groups based on the number of resurfacing implants (bilateral versus unilateral). Results: 41 unilateral and 9 bilateral subjects were enrolled and followed for serum Co and Cr levels. In general, Co/Cr levels were increased at all time points when compared to control levels in both groups. Bilateral subjects had average serum levels concentrations significantly higher than those observed for unilateral cases (Co: 5.99 vs 2.56 μg/L (p=0.0001); Cr: 6.66 vs 3.60 (p=0.0009). Conclusion: Elevated serum Co/Cr levels were observed at all time points following implantation in both groups and serum levels were nearly 2 times higher in the bilateral group. Based on these preliminary findings, patients undergoing bilateral total hip resurfacing arthroplasty may need to be monitored more closely than those patients receiving unilateral devices. In addition, these bilateral cases may be at a greater risk of ion level toxicities than the unilateral population.
Geometrical correction of the e-beam proximity effect for raster scan systems (1999)

Increasing demands on pattern fidelity and CD accuracy in e- beam lithography require a correction of the e-beam proximity effect. The new needs are mainly coming from OPC at mask level and x-ray lithography. The e-beam proximity limits the achievable resolution and affects neighboring structures causing under- or over-exposion depending on the local pattern densities and process settings. Methods to compensate for this unequilibrated does distribution usually use a dose modulation or multiple passes. In general raster scan systems are not able to apply variable doses in order to compensate for the proximity effect. For system of this kind a geometrical modulation of the original pattern offers a solution for compensation of line edge deviations due to the proximity effect. In this paper a new method for the fast correction of the e-beam proximity effect via geometrical pattern optimization is described. The method consists of two steps. In a first step the pattern dependent dose distribution caused by back scattering is calculated by convolution of the pattern with the long range part of the proximity function. The restriction to the long range part result in a quadratic sped gain in computing time for the transformation. The influence of the short range part coming from forward scattering is not pattern dependent and can therefore be determined separately in a second step. The second calculation yields the dose curve at the border of a written structure. The finite gradient of this curve leads to an edge displacement depending on the amount of underground dosage at the observed position which was previously determined in the pattern dependent step. This unintended edge displacement is corrected by splitting the line into segments and shifting them by multiples of the writers address grid to the opposite direction.
Scaling the huygens absorbing boundary condition code on shared memory architecture (2014)

The code of the FDTD method and the Huygens Absorbing Boundary Condition (HABC) is parallelized with OpenMP on shared memory architecture. The parallelisation efficiency of the strong scaling and the weak scaling is presented.