gebhart/patrepeval huggingface dataset:
Infusions of T Cells Armed with Anti-CD3 x Anti-Her2/neu Bispecific Antibody Modulate In Vivo Patient Immune Responses in Phase I Clinical Trials for Breast and Hormone Refractory Prostate Cancers. (2004)

Abstract Phase I dose escalation trials using ex vivo expanded, anti-CD3 activated T cells (ATC) armed with anti-CD3 x anti-Her2/neu (Her2Bi) to evaluate toxicity and immune responses were conducted in 8 Stage IV breast cancer (BrCa), 5 high-risk Stage II BrCa, and 3 hormone refractory prostate cancer (HRPC) patients. Patients received 8 infusions (Inf) twice per week for 4 weeks totaling 40 billion (11/16 patients) or 80 billion (5/16 patients) HER2Bi-armed ATC. Phenotyping the expansion product showed 90.0±10.1% (mean±SD)CD3, 47.5±22.2 CD4, and 41.9±19.9 CD8. Specific lysis of SK-BR-3 targets by patients’ armed ATC (n= 16 patients) at E:T of 10, 5, and 2.5 averaged 54.1±17, 39.5±14, and 25.9±11, respectively. These results were comparable to 63.4±17 (p = 0.23), 57.7±20 (p = 0.09), and 33.9±16 (p = 0.38) specific lysis mediated by armed ATC from 6 normal donors at the respective E:T confirming the function of Her2Bi-armed ATC at the time of Inf. By ELISA, 4/8 (50%) of the patients developed anti-mouse antibody responses (HAMA) to OKT3, which peaked (median: 35.4 ng/ml; range: 4–64 ng/ml) between Inf#5 and Inf#8 (14–27 days post-Inf #1). There were no AEs associated with elevated HAMA titers. Th1/Th2 panels were obtained from patient sera using the Bio-Plex Protein Array System and analyzed as a function of number of Infs. The in vivo T cell response, calculated as the mean Th1[IL-2+IFN-g]/Th2[IL-4+IL-5] ratio of cytokines, showed a polarized Th1 response as a function of armed ATC Inf that increased from 89.1(Inf#1) to 538.6 (Inf #8). Levels of IL-12 also increased by Inf#5 and were constant from Inf#5 through Inf#8 (mean±SD = 34.0±17.2 pg/ml). These findings were consistent with increased CTL responses observed in ELISPOTs of patient post-Inf PBMC exposed to Her2+ tumor targets. Overall immune response, calculated as the average ratio of Th1[IL-2+IFN-g] /Th2 [IL-4+IL-5+IL-10+IL-13], remained Th1 polarized throughout treatment though the ratio decreased as a function of Inf#: going from 9.46 (Inf#1) to 1.42 (Inf #8). TNF-alpha levels were contant from Inf #1–8 (mean±SD = 9.5 ± 4.9 pg/ml), and GM-CSF peaked between Inf #5–8 (92.2 ± 36.4 pg/ml). Detection of MIgG2a+ (anti-CD3 coated) cells in the PBL from 8 patients was highest post-Inf#1 (18.4% ± 16.1) and decreased by Inf #5–8 (4.1% ± 6.1). In 2 patients, MIgG2a+ armed T cells could still be detected 1 week and 3 weeks after Inf#8. All patients received their targeted doses of armed ATC: no dose-limiting toxicities were observed in any patients, and with the exception of a few patients with grade II–III chills/grade II fever, infusions of Her2Bi-armed ATC were well-tolerated. These observations provide evidence that the endogenous immune system is being modulated by the infusion of armed ATC and further support the rationale for performing phase II trials using armed ATC in Her2+ advanced/high risk BrCa and HRPC patients.
In-Situ Ion Milling in the Transmission Electron Microscope (TEM) Outlook to a New Preparation Technique (2001)

Abstract Recent developments in transmission electron microscopy put high demands on specimen preparation. in general the imaging quality is not limited by the performance of the microscope but by the quality of the specimen. in order to achieve a spatial resolution of 0.1 nm in HRTEM undamaged samples with a thickness below 10 nm are required. in energy filtering analytical electron microscopy (EFTEM), a constant specimen thickness over large areas and very low contamination is needed. Conventional ion-milling techniques for TEM specimen preparation are essentially blind. Thus, it is left to chance whether the specimen detail of interest is suitable for TEM-imaging (many specimen areas are too thick). Another problem is the reaction of the specimen with the atmosphere during the transfer from the preparation stage to the microscope, which makes it very difficult to obtain the clean specimen surfaces that are needed in analytical EFTEM. Especially in high-resolution electron microscopy and electron holography the formation of amorphous oxidation and contamination layers on otherwise crystalline materials may seriously reduce the quality of high resolution images of the crystal structure.
Crystallization and preliminary X-ray analysis of a bacterial<scp>L</scp>-amino-acid oxidase from<i>Rhodococcus opacus</i> (2006)

L-Amino-acid oxidases (EC 1.4.3.2) catalyse the stereospecific oxidative deamination of an L-amino-acid substrate to an alpha-keto acid with the production of ammonia and hydrogen peroxide. In this study, the crystallization and preliminary X-ray analysis of a bacterial L-amino-acid oxidase from Rhodococcus opacus (RoLAAO) is described. RoLAAO is a dimeric protein consisting of two identical subunits of 489 amino acids with a calculated molecular weight of 54.2 kDa and a non-covalently bound FAD molecule. RoLAAO was crystallized by the vapour-diffusion method in two different space groups: P2(1)2(1)2(1) (unit-cell parameters a = 65.7, b = 109.7, c = 134.4 A) and C222(1) (unit-cell parameters a = 68.3, b = 88.4, c = 186.6 A). Both crystal forms diffracted X-rays to a resolution of at least 1.6 A.
Recent Advances in Anhydrous Solvents for CO2 Capture: Ionic Liquids, Switchable Solvents, and Nanoparticle Organic Hybrid Materials (2015)

CO2 capture by amine scrubbing, which has a high CO2 capture capacity and a rapid reaction rate, is the most employed and investigated approach to date. There are a number of recent large-scale demonstrations including the Boundary Dam Carbon Capture Project by SaskPower in Canada that have reported successful implementations of aqueous amine solvent in CO2 capture from flue gases. The findings from these demonstrations will significantly advance the field of CO2 capture in the coming years. While the latest efforts in aqueous amine solvents are exciting and promising, there are still several drawbacks to amine-based CO2 capture solvents including high volatility and corrosiveness of the amine solutions, as well as the high parasitic energy penalty during the solvent regeneration step. Thus, in a parallel effort, alternative CO2 capture solvents, which are often anhydrous, have been developed as the third-generation CO2 capture solvents. These novel classes of liquid materials include: Ionic Liquids (ILs), CO2-triggered switchable solvents (i.e., CO2 Binding Organic Liquids (CO2BOLs), Reversible Ionic Liquids (RevILs)), and Nanoparticle Organic Hybrid Materials (NOHMs). This paper provides a review of these various anhydrous solvents and their potential for CO2 capture. Particular attention is given to the mechanisms of CO2 absorption in these solvents, their regeneration and their processability – especially taking into account their viscosity. While not intended to provide a complete coverage of the existing literature, this review aims at pointing the major findings reported for these new classes of CO2 capture media.
Ultrasonic/Sonic Rotary-Hammer Drills (2010)

Ultrasonic/sonic rotary-hammer drill (USRoHD) is a recent addition to the collection of apparatuses based on ultrasonic/sonic drill corer (USDC). As described below, the USRoHD has several features, not present in a basic USDC, that increase efficiency and provide some redundancy against partial failure. USDCs and related apparatuses were conceived for boring into, and/or acquiring samples of, rock or other hard, brittle materials of geological interest. They have been described in numerous previous NASA Tech Briefs articles. To recapitulate: A USDC can be characterized as a lightweight, lowpower, piezoelectrically driven jackhammer in which ultrasonic and sonic vibrations are generated and coupled to a tool bit. A basic USDC includes a piezoelectric stack, an ultrasonic transducer horn connected to the stack, a free mass ( free in the sense that it can bounce axially a short distance between hard stops on the horn and the bit), and a tool bit. The piezoelectric stack creates ultrasonic vibrations that are mechanically amplified by the horn. The bouncing of the free mass between the hard stops generates the sonic vibrations. The combination of ultrasonic and sonic vibrations gives rise to a hammering action (and a resulting chiseling action at the tip of the tool bit) that is more effective for drilling than is the microhammering action of ultrasonic vibrations alone. The hammering and chiseling actions are so effective that unlike in conventional twist drilling, little applied axial force is needed to make the apparatus advance into the material of interest. There are numerous potential applications for USDCs and related apparatuses in geological exploration on Earth and on remote planets. In early USDC experiments, it was observed that accumulation of cuttings in a drilled hole causes the rate of penetration of the USDC to decrease steeply with depth, and that the rate of penetration can be increased by removing the cuttings. The USRoHD concept provides for removal of cuttings in the same manner as that of a twist drill: An USRoHD includes a USDC and a motor with gearhead (see figure). The USDC provides the bit hammering and the motor provides the bit rotation. Like a twist drill bit, the shank of the tool bit of the USRoHD is fluted. As in the operation of a twist drill, the rotation of the fluted drill bit removes cuttings from the drilled hole. The USRoHD tool bit is tipped with a replaceable crown having cutting teeth on its front surface. The teeth are shaped to promote fracturing of the rock face through a combination of hammering and rotation of the tool bit. Helical channels on the outer cylindrical surface of the crown serve as a continuation of the fluted surface of the shank, helping to remove cuttings. In the event of a failure of the USDC, the USRoHD can continue to operate with reduced efficiency as a twist drill. Similarly, in the event of a failure of the gearmotor, the USRoHD can continue to operate with reduced efficiency as a USDC.
Noninvasive Estimation of Respiratory Mechanics in Spontaneously Breathing Ventilated Patients: A Constrained Optimization Approach. (2015)

This paper presents a method for breath-by-breath noninvasive estimation of respiratory resistance and elastance in mechanically ventilated patients. For passive patients, well-established approaches exist. However, when patients are breathing spontaneously, taking into account the diaphragmatic effort in the estimation process is still an open challenge. Mechanical ventilators require maneuvers to obtain reliable estimates for respiratory mechanics parameters. Such maneuvers interfere with the desired ventilation pattern to be delivered to the patient. Alternatively, invasive procedures are needed. The method presented in this paper is a noninvasive way requiring only measurements of airway pressure and flow that are routinely available for ventilated patients. It is based on a first-order single-compartment model of the respiratory system, from which a cost function is constructed as the sum of squared errors between model-based airway pressure predictions and actual measurements. Physiological considerations are translated into mathematical constraints that restrict the space of feasible solutions and make the resulting optimization problem strictly convex. Existing quadratic programming techniques are used to efficiently find the minimizing solution, which yields an estimate of the respiratory system resistance and elastance. The method is illustrated via numerical examples and experimental data from animal tests. Results show that taking into account the patient effort consistently improves the estimation of respiratory mechanics. The method is suitable for real-time patient monitoring, providing clinicians with noninvasive measurements that could be used for diagnosis and therapy optimization.
Robust increase of leaf size by Arabidopsis thaliana GRF3-like transcription factors under different growth conditions (2018)

An increase in crop yield is essential to reassure food security to meet the accelerating global demand. Several genetic modifications can increase organ size, which in turn might boost crop yield. Still, only in a few cases their performance has been evaluated under stress conditions. MicroRNA miR396 repress the expression of GROWTH-REGULATING FACTOR (GRF) genes that codes for transcription factors that promote organ growth. Here, we show that both Arabidopsis thaliana At-GRF2 and At-GRF3 genes resistant to miR396 activity (rGRF2 and rGRF3) increased organ size, but only rGRF3 can produce this effect without causing morphological defects. Furthermore, introduction of At-rGRF3 in Brassica oleracea can increase organ size, and when At-rGRF3 homologs from soybean and rice are introduced in Arabidopsis, leaf size is also increased. This suggests that regulation of GRF3 activity by miR396 is important for organ growth in a broad range of species. Plants harboring rGRF3 have larger leaves also under drought stress, a condition that stimulates miR396 accumulation. These plants also showed an increase in the resistance to virulent bacteria, suggesting that the size increment promoted by rGRF3 occurs without an obvious cost on plant defenses. Our findings indicate that rGRF3 can increase plant organ size under both normal and stress conditions and is a valuable tool for biotechnological applications.
Estimation method of finger tapping dynamics using simple magnetic detection system (2010)

We have developed the simple estimation method of a finger tapping dynamics model for investigating muscle resistance and stiffness during tapping movement in normal subjects. We measured finger tapping movements of 207 normal subjects using a magnetic finger tapping detection system. Each subject tapped two fingers in time with a metronome at 1, 2, 3, 4, and 5 Hz. The velocity and acceleration values for both the closing and opening tapping data were used to estimate a finger tapping dynamics model. Using the frequency response of the ratio of acceleration to velocity of the mechanical impedance parameters, we estimated the resistance (friction coefficient) and compliance (stiffness). We found two dynamics models for the maximum open position and tap position. In the maximum open position, the extensor muscle resistance was twice as high as the flexor muscle resistance and males had a higher spring constant. In the tap position, the flexor muscle resistance was much higher than the extensor muscle resistance. This indicates that the tapping dynamics in the maximum open position are controlled by the balance of extensor and flexor muscle friction resistances and the flexor stiffness, and the flexor friction resistance is the main component in the tap position. It can be concluded that our estimation method makes it possible to understand the tapping dynamics.
A nanomechanical computer—exploring new avenues of computing (2007)

We propose a fully mechanical computer based on nano-electromechanical elements. Our aim is to combine this classical approach with modern nanotechnology to build a nanomechanical computer (NMC) based on nanomechanical transistors. The main motivation behind constructing such a computer is threefold: (i) mechanical elements are more robust to electromagnetic shocks than current dynamic random access memory (DRAM) based purely on complimentary metal oxide semiconductor (CMOS) technology, (ii) the power dissipated can be orders of magnitude below CMOS and (iii) the operating temperature of such an NMC can be an order of magnitude above that of conventional CMOS.
Using G4FETs as a Data Router for In-Plane Crossing of Signal Paths (2007)

Theoretical analysis and some experiments have demonstrated that siliconon- insulator (SOI) 4-gate transistors the type known as G(exp 4)FETs could be efficiently used for in-plane crossing of signal paths. Much of the effort of designing very-large-scale integrated (VLSI) circuits is focused on area-efficient routing of signals. The main source of difficulty in VLSI signal routing is the requirement to prevent crossing, in the same plane, of wires that are meant to be kept electrically insulated from each other. Consequently, it often becomes necessary to design and build VLSI circuits in multiple layers with vias (connections between conductors in different layers at selected locations). Suitable devices that would prevent, or at least sufficiently suppress, undesired electrical coupling (cross-talk) between wires crossing in the same plane would enable compact, simpler implementation complex interconnection networks with in-plane crossings that, heretofore, have not been possible in VLSI circuitry. The use of G4FETs as in-plane signal-crossing devices or routers, in combination with the use of G(exp 4)FETs as universal programmable logic gates, would create opportunities for reducing complexity in VLSI design.
A large data resource of genomic copy number variation across neurodevelopmental disorders (2019)

Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted to identify shared etiology among NDDs, but this is the first genome-wide CNV analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ, 1,838 ASD, 427 ADHD and 222 OCD) and 1,769 family members, mainly parents. We identified rare CNVs, defined as those found in <0.1% of 10,851 population control samples. We found clinically relevant CNVs (broadly defined) in 284 (10.5%) of total subjects, including 22 (10.8%) among subjects with SCZ, 209 (11.4%) with ASD, 40 (9.4%) with ADHD, and 13 (5.6%) with OCD. Among all NDD subjects, we identified 17 (0.63%) with aneuploidies and 115 (4.3%) with known genomic disorder variants. We searched further for genes impacted by different CNVs in multiple disorders. Examples of NDD-associated genes linked across more than one disorder (listed in order of occurrence frequency) are <i>NRXN1</i>, <i>SEH1L</i>, <i>LDLRAD4</i>, <i>GNAL</i>, <i>GNG13</i>, <i>MKRN1</i>, <i>DCTN2, KNDC1</i>, <i>PCMTD2</i>, <i>KIF5A</i>, <i>SYNM</i>, and long non-coding RNAs: <i>AK127244</i> and <i>PTCHD1-AS</i>. We demonstrated that CNVs impacting the same genes could potentially contribute to the etiology of multiple NDDs. The CNVs identified will serve as a useful resource for both research and diagnostic laboratories for prioritization of variants.
Ribotype 027 Clostridium difficile infections with measurable stool toxin have increased lactoferrin and are associated with a higher mortality (2014)

We evaluated clinical and diagnostic indicators of severe C. difficile infection (CDI) and their association with poor clinical outcome. A total of 210 patients positive according to PCR (toxin B: tcdB) were included, with patients having a median age of 62 years and a Charlson co-morbidity index (CI) score of 5. Ninety-one percent (n = 191) were positive by toxigenic culture and 61% (n = 129) had stool toxin. Toxin-positive patients had significantly higher fecal lactoferrin (mean 316 μg/g versus 106 μg/g stool; p < 0.0001). Forty percent of patients (n = 85) were infected with ribotype 027 and significantly more of these patients had measurable stool toxin (79% vs. 50%; p < 0.0001). The mean fecal lactoferrin was significantly higher for toxin-positive 027 CDI compared with the 027 toxin-negative group (317 vs 60 μg/g; p = 0.0014). Ribotype 027 CDI with stool toxin showed a higher all-cause, 100-day mortality compared with non-027 with stool toxin (36 % vs 18%; p = 0.017). Logistic regression univariate analysis for odds ratio (OR) and p values revealed that age (OR = 1.1), intensive care unit treatment (OR = 2.7), CI (OR = 1.2), 027 CDI (OR = 2.1), white blood cell count (OR = 1.0), albumin level (OR = 0.1), and stool toxin-positive 027 CDI (OR = 2.5) were significantly associated with 100-day mortality (p < 0.05). In conclusion, CDI PCR-positive patients with 027 infection and stool toxin have increased lactoferrin and are at an increased risk of death.
New High-Precision Magnetorheological Instrument-Based Method of Polishing Optics (1992)

Recently, the need for fine finishing of optical workpieces has become increasingly important, A variety of polishing methods have been developed to satisfy this need. The traditional mechanical methods of polishing optical workpieces use solid shaped tools, and it's rather difficult to obtain surfaces to be polished not only of mirror quality but also physically undisturbed.
Event-Triggered Electrical Control of Urinary Continence (2005)

Individuals with spinal cord injury or neurological disorders may develop involuntary bladder contraction at low volumes (bladder hyper-reflexia), which can lead to significant health problems. Current devices can eliminate nascent contractions through continuous stimulation, but do not have a means to detect the onset of bladder contraction to stimulate conditionally. The pudendal nerve trunk (PNT) electroneurogram (ENG) has been shown that the ENG could be used as to detect bladder contractions and as an input to a control system to trigger conditional electrical stimulation. The objective of this study is to determine whether event-triggered electrical control of urinary continence allows the bladder to fill to greater volume than continuous control, PNT ENG was the input to the control system and served as a trigger for inhibitory stimulation to maintain continence. Conditional inhibitory stimulation controlled by the PNT ENG allowed the bladder to fill to at least the same volume as continuous stimulation before continence was lost. However, the event-triggered control system had a 65% reduction in stimulation time as compared to continuous stimulation. These results support the use of an event-triggered control system to maintain urinary continence
rDEN2/4Δ30(ME), a Live Attenuated Chimeric Dengue Serotype 2 Vaccine, is Safe and Highly Immunogenic in Healthy Dengue-Naïve Adults (2006)

rDEN2/4Delta30(ME) is an attenuated chimeric dengue virus in which the prM and E structural proteins of the DEN4 candidate vaccine rDEN4Delta30 have been replaced by those of the prototypic DEN2 NGC virus. rDEN2/4Delta30(ME) was evaluated at a dose of 1,000 PFU in 20 healthy dengue-naïve adult volunteers. Eight volunteers received placebo. Volunteers were monitored closely for adverse events and serum was collected for determination of the level and duration of viremia and neutralizing antibody response. The vaccine was well tolerated by all volunteers. The most common adverse events observed were a transient asymptomatic rash and mild neutropenia. All vaccines seroconverted to DEN2 and maintained significant antibody titers throughout the six-month trial duration. Eleven vaccinees had vaccine virus recovered from the blood during the study. RNA derived from virus isolates obtained from viremic volunteers was sequenced for confirmation of retention of the Delta30 mutation in the 3' UTR. The Delta30 mutation remained unchanged in each isolate, confirming the stability of the Delta30 mutation. Further evaluation of this vaccine in a tetravalent formulation is warranted.