gebhart/patrepeval huggingface dataset:
Effect of testosterone on binding of insulin-like growth factor-I (IGF-I) and IGF-II in growing antlers of fallow deer (Dama dama). (1996)

Testosterone regulation of antler growth may be via the insulin-like growth factors (IGFs). Using histological autoradiography we have measured the specific binding of IGF-I and IGF-II to antler sections during normal growth and during the maturation which follows testosterone treatment of adult fallow deer. In antlers from 20 to 100 days following casting, IGF-I binding was constant within each histological region until 80 days. Between this time and 100 days there was decreased binding to chondrocytes (P < or = 0.01) and increased binding to the reserve mesenchyme/perichondrium (P < or = 0.001). Following testosterone treatment, IGF-I binding declined in dermis (P < or = 0.05), reserve mesenchyme/perichondrium (P < or = 0.05), and chondroblasts (P < or = 0.01). Specific binding of IGF-II showed no change during normal or testosterone-stimulated growth. In conclusion, the regulation of antler maturation by testosterone may include IGF action, probably via the Type 1 IGF receptor.
Design and preliminary evaluation of a multi-robotic system with pelvic and hip assistance for pediatric gait rehabilitation (2017)

This paper presents a modular, computationally-distributed "multi-robot" cyberphysical system designed to assist children with developmental delays in learning to walk. The system consists of two modules, each assisting a different aspect of gait: a tethered cable pelvic module with up to 6 degrees of freedom (DOF), which can modulate the motion of the pelvis in three dimensions, and a two DOF wearable hip module assisting lower limb motion, specifically hip flexion. Both modules are designed to be lightweight and minimally restrictive to the user, and the modules can operate independently or in cooperation with each other, allowing flexible system configuration to provide highly customized and adaptable assistance. Motion tracking performance of approximately 2 mm root mean square (RMS) error for the pelvic module and less than 0.1 mm RMS error for the hip module was achieved. We demonstrate coordinated operation of the two modules on a mannequin test platform with articulated and instrumented lower limbs.
To Design Scalable Free Energy Perturbation Networks, Optimal Is Not Enough (2022)

Drug discovery is accelerated with computational methods such as alchemical simulations to estimate ligand affinities. In particular, relative binding free energy (RBFE) simulations are beneficial for lead optimization. To use RBFE simulations to compare prospective ligands in silico, researchers first plan the simulation experiment, represented by graphs where nodes represent ligands and graph edges represent alchemical transformations between ligands. Recent work demonstrated that optimizing the statistical architecture of these perturbation graphs improves the accuracy of the resultant changes in the free energy of ligand binding. Therefore, to improve the success rate of computational drug discovery, we present the open-source software package High Information Mapper (HiMap) --- a modernized take on its predecessor, Lead Optimization Mapper (LOMAP). HiMap removes heuristics decisions from design selection and instead finds statistically optimal graphs over ligands clustered with machine learning. Beyond optimal design generation, we present theoretical insights for designing alchemical perturbation maps. Some of these results include that for n number of nodes, the precision of perturbation maps is stable at n·ln(n) edges. We additionally find that optimal designs will converge more rapidly than radial and LOMAP designs. Moreover, we derive bounds for how clustering reduces cost for designs with a constant expected error, invariant of the size of the design. These results inform how to best design perturbation maps for computational drug discovery and have broader implications for experimental design.
Intracellular drug release nanosystems (2012)

In order to elicit therapeutic effects, many drugs including small molecule anticancer drugs, proteins, siRNA, and DNA have to be delivered and released into the specific cellular compartments typically the cytoplasm or nucleus of target cells. Intracellular environment-responsive nanosystems that exhibit good extracellular stability while rapidly releasing drugs inside cancer cells have been actively pursued for effective cancer therapy. Here, we highlight novel designs of smart nanosystems that release drugs in response to an intracellular biological signal of cancer cells such as acidic pH in endo/lysosomal compartments, enzymes in lysosomes, and redox potential in cytoplasm and the cell nucleus.
Establishing the Socio-Economic Impact of Degenerative Cervical Myelopathy Is Fundamental to Improving Outcomes [AO Spine RECODE-DCM Research Priority Number 8] (2022)

A clear quantification of the impact of DCM is needed to raise the profile of a common and disabling condition. Current evidence suggests this is likely to be globally substantial.
Effect of polyisocyanate hardener on adhesive force of waterborne polyurethane adhesives (2007)

Abstract A series of waterborne polyurethane (WBPU)/hardener adhesives were obtained from mixing of WBPU containing different types of polyol as a soft segment with aliphatic and aromatic polyisocyanates hardeners. By characterization of allophanate and biuret bonds formed from the reaction of hardener NCO with urethane/urea groups of WBPU using 1 HNMR spectroscopy. It was found that the optimum number ratio (molar ratio) of NCO group of hardener to urethane/urea group of WBPU that shows the highest adhesion force was depended on the type of hardener (aliphatic/aromatic polyisocyanate) and dimethylol propionic acid (DMPA) content (total content of urethane/urea groups); however independent of the type of soft segment (polyol) of WBPU. The optimum number ratio (molar ratio) of NCO group of aromatic polyisocyanate hardener to urethane/urea was higher than that of aliphatic hardener to achieve the highest adhesion force of WBPU. The adhesive force increased with increasing hardener content up to the optimum point and then decreased. Poly(tetramethylene adipate glycol) (PTAd) based WBPUs with aliphatic hardener show higher adhesive force than Poly(tetramethylene oxide glycol) (PTMG) and aliphatic hardener‐based WBPUs at the optimum number ratio (molar ratio) of NCO group of hardener to urethane/urea group of WBPU. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 3663–3669, 2007
<title>Time-gated imaging with femtosecond transillumination optical coherence tomography</title> (1993)

We describe a new technique called femtosecond transillumination optical coherence tomography which combines femtosecond pulses, coherent heterodyne detection, and fiber- optic confocal imaging to achieve time-gated and spatially resolved imaging through diffusive biological tissue. Images of absorbing objects embedded in scattering biological media are demonstrated by selecting either the earliest arriving unscattered ballistic component or the least scattered portion of the diffuse transmitted light. Time and spatially resolved analysis of photon migration through model scattering systems is used to establish fundamental limits for this class of time-gated and spatially resolved optical imaging techniques, and to evaluate their potential biomedical applications in early tumor diagnosis.
Molecular detection of pancreatic neuroendocrine tumors using methylated DNA markers: Discovery and tissue validation. (2020)

e16705 Background: The prevalence of pancreatic neuroendocrine tumors (PNETs) has increased in the last decade. Despite being clinically asymptomatic PNETs can be biologically aggressive. There is currently no reliable non-invasive diagnostic biomarker for PNETs. In this study we aimed to identify and validate methylated DNA marker (MDM) candidates that differentiate PNET from normal pancreas. Methods: For discovery, reduced representation bisulfite sequencing (RRBS) was performed on DNA extracted from frozen normal pancreas (n = 13) and PNET (n = 51) tissues. Area under the receiver operator characteristic curve (AUC), fold-change, and p-value criteria selected candidates MDMs for blinded validation in independent FFPE tissues from primary PNET (n = 67; solid = 50, cystic = 17), normal pancreas controls (n = 24), and normal buffy coat (n = 36) using methylation specific PCR. MDM distributions in primary PNETs were compared to primary lung (n = 36) and small bowel (n = 36) NETs and metastatic PNET tissue (n = 25). The discrimination accuracy of candidate markers was summarized as the AUC with corresponding 95% confidence intervals (CI). Results: From the RRBS discovery, 31 candidate MDMs were selected for validation. Four MDMs ( SRRM3, HCN2, SPTBN4 and TMC6) achieved individual AUCs ≥0.95 in the validation set (Table). These MDMs were similarly discriminant in metastatic PNET tissue and in primary lung and small bowel NETs. Three out of these 4 MDMs perfectly differentiated PNET tissue from buffy coat with AUC of 1 and may be ideally suited for further development of a blood-based assay. Conclusions: We identified and validated novel MDMs in tissue that discriminate PNETs from controls with normal pancreas and buffy coat with high accuracy. These MDMs also differentiated metastatic PNETs from normal pancreas tissue. Further exploration of these candidate tissue MDMs in plasma can potentially guide diagnosis and management of PNETs. Funding: P30DK084567. [Table: see text]
Novel glycylated sugar alcohols protect ESC-specific microRNAs from degradation in iPS cells (2016)

Excessive accumulation of embryonic stem cell (ESC)-specific microRNAs occurs in both ESCs and induced pluripotent stem cells (iPSC); yet, the mechanism involved is unknown. In iPSCs, we for the first time found that novel glycylated sugar alcohols, particularly glycylglycerins, are tightly bound with ESC-specific microRNA precursors (pre-miRNA), such as pre-miR-302. Among these isolated glycylglycerins, we further identified that 1,3-diglycylglycerin and 1,2,3-triglycylglycerin are two major compounds bonded with negatively charged nucleic acids via electro-affinity and subsequently forming sugar-like coats in the hairpin-like double helix structures of pre-miRNAs. As a result, such glycylglycerin-formed coating serves as a protection layer against miRNA degradation. Moreover, we found that the pH value of iPSC cytosol determines the charges of these glycylglycerins. During iPSC differentiation, the cytosol pH is increased and hence neutralizes the charges of glycylglycerins, consequently leading to fast miRNA degradation. Therefore, the current findings not only explain how ESC-specific miRNAs are preserved and accumulated in iPSCs and ESCs but also demonstrate an important function of glycylglycerins in protecting the structural integrity of highly degradable miRNAs, providing a useful means for maintaining miRNA/siRNA function as well as developing the related RNA interference (RNAi) applications.
Transparent Fiber–Millimeter-Wave–Fiber System in 100-GHz Band Using Optical Modulator and Photonic Down-Conversion (2022)

We demonstrate the first fiber–millimeter-wave–fiber system in the 100-GHz band using a low-loss optical modulator and direct photonic down-conversion technology. The utilization of a low-loss optical modulator for the direct conversion of a millimeter-wave signal to an optical signal significantly simplifies the millimeter-wave radio receiver because it includes only a radio front-end and an optical modulator. In addition, by adopting direct photonic down-conversion technology for simultaneous detection and down-conversion of the millimeter-wave signal to the microwave band, the fiber–radio receiver and subsequent digital signal processing can be considerably simplified. Using the proposed technologies, we successfully transmitted 32-/64-quadrature amplitude modulation orthogonal frequency division multiplexing and single-carrier signal with a line rate of 71.4 Gb/s and a net data rate of 53.7 Gb/s over a wired and wireless converged system consisting of two optical fiber links and a 20 m radio link at 101 GHz. The proposed system is promising for high-capacity, low-latency, and low-power consumption fiber-wireless transmission in beyond 5G networks.
Protection against toxic amyloid-beta oligomers by PMN310, a monoclonal antibody rationally designed for greater therapeutic potency in Alzheimer’s disease (P1-6.006) (2023)

Evaluate the protective activity of PMN310 against toxic amyloid-beta oligomers (AßO) in vitro and in vivo
Growth Differentiation Factor-9 Promotes the Growth, Development, and Survival of Human Ovarian Follicles in Organ Culture (2002)

Growth differentiation factor-9 (GDF-9) is a growth factor and a member of the TGFbeta superfamily that is secreted by oocytes in growing ovarian follicles. In the current study we cultured human ovarian follicles within slices of ovarian cortical tissue in the presence and absence of recombinant rat GDF-9. Ovarian tissue was obtained by biopsy during cesarean section (31 women) or gynecological laparoscopy (3 women). The mean age (+/-SD) of the women who donated tissue was 32.8 +/- 5.0 yr (range, 19-41 yr). In these biopsies a total of 900 follicles were analyzed. A significantly higher proportion of cultured primordial follicles showed growth initiation and reached the secondary stage of development in the presence of GDF-9. In serum-free cultures after 7 d, 53% of the follicles had reached the secondary stage with GDF-9 vs. 31% in the control group (P < 0.01). Follicle viability was also improved in the presence of GDF-9 after 7 d in culture (74% GDF-9 vs. 48% control), which resulted in a smaller reduction in follicle numbers due to atresia. Treatment with GDF-9 in vitro promoted the survival and progression of human follicular development to the secondary stage. This oocyte-derived factor may be essential for the development of somatic cells in early human follicles and useful in designing culture conditions for maturation of follicles and oocytes in vitro.
Widely tunable mid-infrared quantum cascade lasers using sampled grating reflectors (2012)

We demonstrate a three-section, electrically pulsed quantum cascade laser which consists of a Fabry-Pérot section placed between two sampled grating distributed Bragg reflectors. The device is current-tuned between ten single modes spanning a range of 0.46 μm (63 cm(-1)), from 8.32 to 8.78 μm. The peak optical output power exceeds 280 mW for nine of the modes.
ChemInform Abstract: 3,4‐DIMETHYLPHOSPHOLYLMAGNESIUM AND ‐CADMIUM DERIVATIVES: SYNTHESIS AND THEIR USE IN THE PREPARATION OF NEW PHOSPHOLES WITH PHOSPHORUS‐FUNCTIONAL SUBSTITUENTS (1981)

Abstract Durch Reaktion des Phosphols (I) mit Na/Naphtalin (II) oder Lithium‐ Metall und anschließende Umsetzung mit den Alkylhalogeniden (III) kann man nach Oxidation mit Schwefel die P‐Alkylphospholsulfide (IV) gewinnen.
Patient-derived extracellular matrix demonstrates role of COL3A1 in blood vessel mechanics (2023)

Vascular Ehlers-Danlos Syndrome (vEDS) is a rare autosomal dominant disease caused by mutations in the COL3A1 gene, which renders patients susceptible to aneurysm and arterial dissection and rupture. To determine the role of COL3A1 variants in the biochemical and biophysical properties of human arterial ECM, we developed a method for synthesizing ECM directly from vEDS donor fibroblasts. We found that the protein content of the ECM generated from vEDS donor fibroblasts differed significantly from ECM from healthy donors, including upregulation of collagen subtypes and other proteins related to ECM structural integrity. We further found that ECM generated from a donor with a glycine substitution mutation was characterized by increased glycosaminoglycan content and unique viscoelastic mechanical properties, including increased time constant for stress relaxation, resulting in a decrease in migratory speed of human aortic endothelial cells when seeded on the ECM. Collectively, these results demonstrate that vEDS patient-derived fibroblasts harboring COL3A1 mutations synthesize ECM that differs in composition, structure, and mechanical properties from healthy donors. These results further suggest that ECM mechanical properties could serve as a prognostic indicator for patients with vEDS, and the insights provided by the approach demonstrate the broader utility of cell-derived ECM in disease modeling. STATEMENT OF SIGNIFICANCE: The role of collagen III ECM mechanics remains unclear, despite reported roles in diseases including fibrosis and cancer. Here, we generate fibrous, collagen-rich ECM from primary donor cells from patients with vascular Ehlers-Danlos syndrome (vEDS), a disease caused by mutations in the gene that encodes collagen III. We observe that ECM grown from vEDS patients is characterized by unique mechanical signatures, including altered viscoelastic properties. By quantifying the structural, biochemical, and mechanical properties of patient-derived ECM, we identify potential drug targets for vEDS, while defining a role for collagen III in ECM mechanics more broadly. Furthermore, the structure/function relationships of collagen III in ECM assembly and mechanics will inform the design of substrates for tissue engineering and regenerative medicine.
Durable Control of HIV-1 Using a Staphylococcus aureus Cas9-Expressing Lentivirus Co-Targeting Viral Latency and Host Susceptibility (2020)

Abstract CRISPR/Cas9 gene editing has the potential to revolutionize the clinical management of HIV-1 infection, and may eliminate the need for antiretroviral therapy (ART). Current gene therapies attempt to either excise HIV-1 provirus or target HIV-1 entry receptors to prevent infection of new cells. Using a viral dynamic model, we determined that combining these two interventions, in the presence or absence of ART, significantly lowers the gene editing efficacy thresholds required to achieve an HIV-1 cure. To implement this dual-targeting approach, we engineered a single lentiviral vector that simultaneously targets multiple highly-conserved regions of the provirus and the host CXCR4 coreceptor, and developed a novel coculture system enabling real-time monitoring of latent infection, viral reactivation, and infection of new target cells. Simultaneous dual-targeting depleted HIV-1-infected cells with significantly greater potency than vectors targeting either virus or host independently, highlighting its potential as an HIV-1 cure strategy.
Multi-Agent Deep Reinforcement Learning Multiple Access for Heterogeneous Wireless Networks with Imperfect Channels (2020)

This paper investigates a futuristic spectrum sharing paradigm for heterogeneous wireless networks with imperfect channels. In the heterogeneous networks, multiple wireless networks adopt different medium access control (MAC) protocols to share a common wireless spectrum and each network is unaware of the MACs of others. This paper aims to design a distributed deep reinforcement learning (DRL) based MAC protocol for a particular network, and the objective of this network is to achieve a global $α$-fairness objective. In the conventional DRL framework, feedback/reward given to the agent is always correctly received, so that the agent can optimize its strategy based on the received reward. In our wireless application where the channels are noisy, the feedback/reward (i.e., the ACK packet) may be lost due to channel noise and interference. Without correct feedback, the agent (i.e., the network user) may fail to find a good solution. Moreover, in the distributed protocol, each agent makes decisions on its own. It is a challenge to guarantee that the multiple agents will make coherent decisions and work together to achieve the same objective, particularly in the face of imperfect feedback channels. To tackle the challenge, we put forth (i) a feedback recovery mechanism to recover missing feedback information, and (ii) a two-stage action selection mechanism to aid coherent decision making to reduce transmission collisions among the agents. Extensive simulation results demonstrate the effectiveness of these two mechanisms. Last but not least, we believe that the feedback recovery mechanism and the two-stage action selection mechanism can also be used in general distributed multi-agent reinforcement learning problems in which feedback information on rewards can be corrupted.
A Vector Space Model on Hierarchical Structures with Dynamic Mapping Operator Creation (2008)

We develop a new vector space model of a hierarchical structure depending on a user's viewpoint by performing dynamic mapping operator creation. In order to determine appropriate relationships among information resources, it is important to develop a correlation computation method that depends on the hierarchical structure. Our method determines the correlation in vector space corresponding to the hierarchical structure by dynamic mapping operator creation; this mapping operator represents the hierarchical structure depending on the user's viewpoint by simple matrix computing. Furthermore, our method determines the correlations according to user's viewpoints by dynamic mapping operator creation on the basis of the hierarchical structure. It helps to obtain various information resources related to a query depending on the hierarchical structure and user's viewpoints.
Autonomous system for pathogen detection and identification (1998)

This purpose of this project is to build a prototype instrument that will, running unattended, detect, identify, and quantify BW agents. In order to accomplish this, we have chosen to start with the world' s leading, proven, assays for pathogens: surface-molecular recognition assays, such as antibody-based assays, implemented on a high-performance, identification (ID)-capable flow cytometer, and the polymerase chain reaction (PCR) for nucleic-acid based assays. With these assays, we must integrate the capability to: l collect samples from aerosols, water, or surfaces; l perform sample preparation prior to the assays; l incubate the prepared samples, if necessary, for a period of time; l transport the prepared, incubated samples to the assays; l perform the assays; l interpret and report the results of the assays. Issues such as reliability, sensitivity and accuracy, quantity of consumables, maintenance schedule, etc. must be addressed satisfactorily to the end user. The highest possible sensitivity and specificity of the assay must be combined with no false alarms. Today, we have assays that can, in under 30 minutes, detect and identify simulants for BW agents at concentrations of a few hundred colony-forming units per ml of solution. If the bio-aerosol sampler of this system collects 1000 Ymin and concentrates the respirable particles into 1 ml of solution with 70% processing efficiency over a period of 5 minutes, then this translates to a detection/ID capability of under 0.1 agent-containing particle/liter of air.
Investigation of Mg Doping Profile in the <I>p</I>-Cladding Layer for High-Brightness AlGaInP-Based Light Emitting Diodes (2014)

We investigated 590 nm light-emitting diodes appropriate for full-color display applications in terms of their electrical and optical behaviors during operation according to their Mg doping profile in the p-cladding layer. As the hole concentration in the "b" zone of the p-cladding layer is increased from 3.4 x 10(17) to 6.7 x 10(17), the light output power increases by 41% due to the enhancement of the hole injection into the active region and also due to the minimization of the carrier overflow problem. However, at an oversaturation of Mg doping with excess [Cp2Mg]/[III] in the "b" zone, the internal quantum efficiency degrades because of the decrease in hole concentration because of the oversaturated material problem.