gebhart/patrepeval huggingface dataset:
Remote Ischemic Preconditioning in Human Coronary Artery Bypass Surgery (2010)

Background— We assessed whether remote ischemic preconditioning (RIPC) improves myocardial, renal, and lung protection after on-pump coronary surgery. Methods and Results— This was a single-center, prospective, randomized (1:1), placebo-controlled trial. Patients, investigators, anesthetists, surgeons, and critical care teams were blinded to group allocation. Subjects received RIPC (or placebo) stimuli (×3 upper limb (or dummy arm), 5-minute cycles of 200 mm Hg cuff inflation/deflation) before aortic clamping. Anesthesia, perfusion, cardioplegia, and surgical techniques were standardized. The primary end point was 48-hour area under the curve (AUC) troponin T (cTnT) release. Secondary end points were 6-hour and peak cTnT, ECG changes, cardiac index, inotrope and vasoconstrictor use, renal dysfunction, and lung injury. Hospital survival was 99.4%. Comparing placebo and RIPC, median (interquartile range) AUC 48-hour cTnT (ng/mL −1 /48 h −1 ); 28 (19, 39) versus 30 (22, 38), 6-hour cTnT (ng/mL −1 ); 0.93(0.59, 1.35) versus 1.01(0.72, 1.43), peak cTnT (ng/mL −1 ); 1.02 (0.74, 1.44) versus 1.04 (0.78, 1.51), de novo left bundle-branch block (4% versus 0%) and Q waves (5.3% versus 5.5%), serial cardiac indices, intraaortic balloon pump usage (8.5% versus 7.5%), inotrope (39% versus 50%) and vasoconstrictor usage (66% versus 64%) were not different. Dialysis requirement (1.2% versus 3.8%), peak creatinine (median [interquartile range], 1.2 mg/dL −1 (1.1, 1.4) versus 1.2 (1.0, 1.4)), and AUC urinary albumin-creatinine ratios 69 (40, 112) versus 58 (32, 85) were not different. Intubation times; median (interquartile range), 937 minutes(766, 1402) versus 895(675, 1180), 6-hour; 278 (210, 338) versus 270 (218, 323) and 12-hour pO 2 :FiO 2 ratios 255 (195, 323) versus 263 (210, 308) were similar. Conclusions— In contrast to prior smaller studies, RIPC did not reduce troponin release, improve hemodynamics, or enhance renal or lung protection. Clinical Trial Registration— URL: http://www.ukcrn.org.uk. Unique identifier: 4659.
The crystal structure of the molecular cocrystal L-malic acid L-tartaric acid (1/1) (1996)

Abstract The synthesis and X-ray single crystal structure determination of the molecular cocrystal L-malic acid L-tartaric acid (1/1) 1, the first example of a dimeric cocrystal incorporating two aliphatic car-boxylic acids, are reported. [C4H6O5][C4H6O6], triclinic, P1, a = 4.835(1), b = 6.488(1), c = 9.227(1) Å, α = 73.83(1), β = 88.32(1), γ = 77.32°, V = 271.06(8) Å3, Z = 1, D calc = 1.741 Mg m−3, T = 123(2) K, μ(Mo-Kα) = 0.169 mm−1. A total of 1238 reflections were measured and 1181 unique reflections were used in the refinement. The final parameters for observed data were R = 0.030, R 2 w = 0.085 and R = 0.033, R 2 w = 0.134 for all data. The competition between complimentary hydrogen-bond sites of the two acids, which results in the unexpected heteromeric complex, is discussed, and the observed packing arrangements, and the structural consequences arising from the presence of the extended hydrogen-bond networks, are examined in detail.
Prognostic Role of Serum Parathyroid Hormone Levels in Advanced Prostate Cancer Patients Undergoing Zoledronic Acid Administration (2012)

Secondary hyperparathyroidism has a negative prognostic impact in metastatic prostate cancer patients undergoing zoledronic acid administration. Counteracting elevated PTH levels by adequate doses of vitamin D may improve the efficacy of this drug.
Iterative pose estimation using coplanar points (2002)

A new method is presented for the computation of the position and orientation of a camera with respect to a known object, using four or more coplanar feature points. Starting under the scaled orthographic projection approximation, this method iteratively refines up to two different pose estimates, and provides associated quality measures. When the distance of the object to the camera is large, or when the accuracy of the feature point extraction is low, both pose estimates are plausible.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Optimizing Radioimmunotherapy by Matching Dose Distribution with Tumor Structure using 3D Reconstructions of Serial Images (2001)

The biological effect of radioimmunotherapy (RIT) is most commonly assessed in terms of the absorbed radiation dose. In tumor, conventional dosimetry methods assume a uniform radionuclide and calculate a mean dose throughout the tumor. However, the vasculature of solid tumors tends to be highly irregular and the systemic delivery of antibodies is therefore heterogeneous. Tumor-specific antibodies preferentially localize in the viable, radiosensitive parts of the tumor whereas non-specific antibodies can penetrate into the necrosis where the dose is wasted. As a result, the observed biological effect can be very different to the predicted effect from conventional dose estimates. The purpose of this study is to assess the potential for optimizing the biological effect of RIT by matching the dose-distribution with tumor structure through the selection of appropriate antibodies and radionuclides. Storage phosphor plate technology was used to acquire images of the antibody distribution in serial tumor sections. Images of the distributions of a trivalent (TFM), bivalent (A5B7-IgG), monovalent (MFE-23) and a non-specific antibody (MOPC) were obtained. These images were registered with corresponding images showing tumor morphology. Serial images were reconstructed to form 3D maps of the antibody distribution and tumor structure. Convolution of the image of antibody distribution with beta dose point kernals generated dose-rate distributions for 14C, 131I and 90Y. These were statistically compared with the tumor structure. The highest correlation was obtained for the multivalent antibodies combined with 131I, due to specific retention in viable areas of tumor coupled with the fact that much of the dose was deposted locally. With decreasing avidity the correlation also decreased and with the non-specific antibody this correlation was negative, indicating higher concentrations in the necrotic regions. In conclusion, the dose distribution can be optimized in tumor by selecting the appropriate antibodies and radionuclides. This has the potential to lead to a considerable enhancement of the efficacy of RIT in the clinic.
Measurement and imaging of birefringence and optic axis orientation by phase resolved polarization sensitive optical coherence tomography (2001)

We present an improved method of polarization sensitive optical coherence tomography that enables measurement and imaging of backscattered intensity, birefringence, and fast optic axis orientation simultaneously with only one single A-scan per transverse measurement location. While intensity and birefringence data are obtained in a conventional way, the optic axis orientation is determined from the phase difference recorded in two orthogonal polarization channels. We report on accuracy and precision of the method by measuring birefringence and optic axis orientation of well defined polarization states in a technical object and present maps of birefringence and, what we believe for the first time, of optic axis orientation in biological tissue.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-1 and receptor-2 agonists for cancer therapy (2009)

Ongoing clinical trials will provide important information regarding the future development of TRAIL-R agonists.
Platelet-derived collagenase inhibitor: characterization and subcellular localization. (1985)

Purified human platelets were found to contain a collagenase inhibitor that is immunologically, functionally, and chromatographically identical to that produced by human skin fibroblasts. None of the other formed elements of the blood (erythrocytes, granulocytes, mononuclear cells) possessed detectable quantities of this protein. Virtually all the collagenase inhibitor contained within platelets was released following platelet activation with thrombin. Similarly, platelet activation accompanying blood clotting also resulted in the release of this protein, the ratio of plasma to serum inhibitor levels being approximately equal to 0.5. When platelets were subjected to subcellular fractionation, essentially all of the platelet-associated collagenase inhibitor was found to be located in the alpha-granule. Studies with radiolabeled inhibitor failed to detect uptake of inhibitor by platelets. Furthermore, immunologically reactive protein of similar quantity to that found in platelets was identified in human megakaryocyte lysates. Thus, the data suggest that the collagenase inhibitor is endogenously produced and stored within platelet alpha-granules. The platelet-derived collagenase inhibitor was antigenically identical to the collagenase inhibitor from human skin fibroblasts in double immunodiffusion and, like its fibroblast counterpart, inhibited collagenase on a 1:1 stoichiometric basis. When subjected to several of the chromatographic procedures utilized to purify the fibroblast protein, the platelet inhibitor behaved in an indistinguishable manner. Platelet factor 4, previously reported to be a collagenase inhibitor, was found to be immunologically unrelated to the platelet-derived collagenase inhibitor. Furthermore, platelet factor 4 displayed no collagenase inhibitory activity. Although the function of platelet-derived collagenase inhibitor is unknown, such a protein released by activated platelets may serve to regulate collagen turnover during the early stages of the inflammatory process.
Fabrication of multilayer systems combining microfluidic and microoptical elements for fluorescence detection (2001)

This paper presents the fabrication of a microchemical chip for the detection of fluorescence species in microfluidics. The microfluidic network is wet-etched in a Borofloat 33 (Pyrex) glass wafer and sealed by means of a second wafer. Unlike other similar chemical systems, the detection system is realized with the help of microfabrication techniques and directly deposited on both sides of the microchemical chip. The detection system is composed of the combination of refractive microlens arrays and chromium aperture arrays. The microfluidic channels are 60 /spl mu/m wide and 25 /spl mu/m deep. The utilization of elliptical microlens arrays to reduce aberration effects and the integration of an intermediate (between the two bonded wafers) aluminum aperture array are also presented. The elliptical microlenses have a major axis of 400 /spl mu/m and a minor axis of 350 /spl mu/m. The circular microlens diameters range from 280 to 300 /spl mu/m. The apertures deposited on the outer chip surfaces are etched in a 3000-/spl Aring/-thick chromium layer, whereas the intermediate aperture layer is etched in a 1000-/spl Aring/-thick aluminum layer. The overall thickness of this microchemical system is less than 1.6 mm. The wet-etching process and new bonding procedures are discussed. Moreover, we present the successful detection of a 10-nM Cy5 solution with a signal-to-noise ratio (SNR) of 21 dB by means of this system.
Sensing and Manipulation Problems in Endoscopic Surgery: Experiment, Analysis, and Observation (1993)

The minimally invasive nature of endoscopic surgery allows operations to be performed through small incisions, producing significantly less damage to good tissue than in conventional open surgery. Patient recovery times are thus greatly reduced. This major advantage has driven a dramatic growth of endoscopic techniques in a wide range of surgical applications. Unfortunately, the surgeon's abilities are severely hampered by the limitations of current endoscopic technology. In many ways endoscopic surgery is similar to teleoperation of a remote manipulator. Although the surgeon is physically close to the patient, the surgical environment is effectively “remote,” with sensing and manipulation transmitted through the endoscope and long instruments. Existing solutions from teleoperation applications could likely be applied to endoscopic surgery. This paper attempts to identify the major problems of current endoscopic technology, particularly in vision and manipulation. Vision issues are discussed in the first half, motivated by an experiment comparing surgeons' performance under different visual conditions. Surgeon subjects perform a three-dimensional positioning task with binocular direct vision, monocular direct vision, and a video endoscope. The lack of a stereoscopic view through the endoscope significantly slows performance of the tasks, but there are additional factors that make endoscopic viewing worse than monocular direct viewing. Relevant previous results which demonstrate the significance of interocular spacing in stereo viewing and the effect of display-control axes misalignment are also discussed. Issues of endoscopic manipulation are discussed in the second half of this paper, motivated by a suturing task comparing surgeons' performance with hand and endoscopic instruments. The constraint of endoscopic instruments' passing through the skin reduces their usable degrees of freedom and significantly increases the time to tie a suture knot. Kinematics of endoscopic instruments are compared to the human hand and arm. A model of the surgeon's precision grasp demonstrates the role of stiffness in fine motion control as an example of an advantage of the hand which is lost in the use of endoscopic instruments. The work described in this paper represents an initial effort in identifying problems and evaluating solutions in endoscopic surgery based on objective measurement of performance.
Aid and the resource curse : how can aid be designed to preserve institutions? (2005)

Many studies have found that countries with abundant natural resources grow more slowly than those withouta phenomenon often known as the resource curse or the curse of oil. Some development specialists are concerned that foreign aid may also cause a resource curse. Recent research is not conclusive, but certainly does not rule out the possibility. This Note suggests ways to avoid this risk and urges more attention be devoted to it.
Androgen Receptor Signaling in Androgen-Refractory Prostate Cancer (2001)

Prostate cancer is the second most prevalent cancer in males in the United States. Standard therapy relies on removing, or blocking the actions of, androgens. In most cases, this therapy results in a regression of the cancer because the prostate and most primary prostate tumors depend on androgens for growth and the avoidance of apoptosis. However, a portion of the cancers eventually relapse, at which point they are termed "androgen refractory" and can no longer be cured by conventional therapy of any type. The precise molecular events that lead from androgen-sensitive prostate cancer to androgen-refractory prostate cancer are, therefore, of great interest. This review seeks to identify specific molecular events that may be linked directly to the progression to androgen-refractory cancer. Some of the mechanisms appear to involve the androgen receptor (AR) directly and include mutations in, or amplification of, the AR gene in a manner that allows the AR to respond to low doses of androgens, other steroids, or antiandrogens. In a less direct manner, coactivators may increase the sensitivity of the AR to androgens and even other nonandrogenic substances through a number of mechanisms. Additional indirect mechanisms that do not result from mutation of the AR may involve activation of the AR by peptide growth factors or cytokines or may involve bypassing the AR entirely via other cellular pathways. Identification of the role of these mechanisms in the progression to androgen-refractory prostate cancer is critical for developing therapies capable of curing this disease.
In Vivo Generated Th1 Cells Can Migrate to B Cell Follicles to Support B Cell Responses (2004)

The description of Th1 and Th2 T cell subsets rationalized the inverse correlation between humoral and cell-mediated immunity. Although Th1 cells were described to support cell-mediated immune responses, their role in supporting certain B cell responses was firmly established. However, there is now a prevailing preconception that provision of B cell help is entirely the domain of Th2 cells and that Th1 cells lack this capacity. Previous studies demonstrated that immunization using aluminum hydroxide adjuvants induces Ag-specific Th2 responses, whereas incorporation of IL-12 with aluminum hydroxide produces a Th1 inducing adjuvant. By immunizing TCR transgenic recipient mice in this fashion, we have generated Ag-specific, traceable Th1 and Th2 cells in vivo and assessed their follicular migration and ability to support B cell responses. In this study we have shown that in vivo polarized Th1 and Th2 cells clonally expand to similar levels and migrate into B cell follicles in which they support B cell responses to a similar degree. Critically, we present direct evidence that in vivo polarized, IFN-gamma secreting Th1 cells migrate into B cell follicles where they can interact with Ag-specific B cells.
A coiled-coil oligomerization domain of Bcr is essential for the transforming function of Bcr-Abl oncoproteins. (1993)

In Philadelphia chromosome-positive human leukemias, the c-abl proto-oncogene on chromosome 9 becomes fused to the bcr gene on chromosome 22, and chimeric Bcr-Abl proteins are produced. The fused Bcr sequences activate the tyrosine kinase, actin-binding, and transforming functions of Abl. Activation of the Abl transforming function has been shown to require two distinct domains of Bcr: domain 1 (Bcr amino acids 1 to 63) and domain 2 (Bcr amino acids 176 to 242). The amino acid sequence of domain 1 indicates that it may be a coiled-coil oligomerization domain. We show here that domain 1 of Bcr forms a homotetramer. Tetramerization of Bcr-Abl through Bcr domain 1 correlates with activation of the tyrosine kinase and F-actin-binding functions of Abl. Disruption of the coiled coil by insertional mutagenesis inactivates the oligomerization function as well as the ability of Bcr-Abl to transform Rat-1 fibroblasts or to abrogate interleukin-3 dependence in lymphoid cells. These results strongly suggest that Bcr-Abl oligomers are the active entities in transformation.
Noninvasive Molecular Imaging Using Reporter Genes (2013)

Noninvasive reporter gene imaging is a component of molecular imaging. Reporter imaging can provide noninvasive assessments of endogenous biologic processes in living subjects and can be performed using different imaging modalities. This review will focus on radionuclide-based reporter gene imaging as developed and applied in preclinical and clinical studies. Examples of different reporter systems are presented, with a focus on human reporter systems. Selected applications are discussed, including adoptive cell therapies, gene and oncoviral therapies, oncogenesis, signal pathway monitoring, and imaging drug treatment. Molecular imaging, and noninvasive reporter gene imaging in particular, are making important contributions to our understanding of disease development, progression, and treatment in our current era of molecular medicine and individualized patient care.
Formulation Stabilization and Disaggregation of Bevacizumab, Ranibizumab and Aflibercept in Dilute Solutions (2018)

We developed a novel formulation that significantly stabilizes mAbs under unfavorable conditions such as low concentration or body temperature. The formulation allows for tissue permeation experimentation. The formulation also exhibits a disaggregating effect on mAbs, which can be applied to the manufacture/packaging of mAbs and bioassay reagents.
Rigidity of fibrin gels as measured by quasielastic light scattering (1980)

Abstract The strength of fibrin gels has been investigated by a recently developed laser light scattering technique for determining the shear modulus of soft gels. By this method, changes in the modulus were monitored as a function of time without perturbing the material. Fibrin gels were crosslinked with blood coagulation factor XIII. Rigidity measurements and SDS–polyacrylamide gel electrophoresis were used to correlate gel strength with the number of covalently bonded subunit chains. The modulus was found to vary linearly with the number of crosslinks until maximum rigidity was achieved.
Caspase-1 enhances the apoptotic response of prostate cancer cells to ionizing radiation. (2004)

The present study provides an initial mechanistic insight into the functional involvement of caspase-1 in changing the apoptotic threshold of prostate cancer cells to radiation. These findings will enhance the understanding of the molecular basis of prostate tumor radioresistance and may have significant clinical relevance in improving the therapeutic index of radiotherapy in prostate cancer patients.
A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus (2010)

RNA interference (RNAi) is a natural mechanism regulating protein expression that is mediated by small interfering RNAs (siRNA). Harnessing RNAi has potential to treat human disease; however, clinical evidence for the effectiveness of this therapeutic approach is lacking. ALN-RSV01 is an siRNA directed against the mRNA of the respiratory syncytial virus (RSV) nucleocapsid (N) protein and has substantial antiviral activity in a murine model of RSV infection. We tested the antiviral activity of ALN-RSV01 in adults experimentally infected with wild-type RSV. Eighty-eight healthy subjects were enrolled into a randomized, double-blind, placebo-controlled trial. A nasal spray of ALN-RSV01 or saline placebo was administered daily for 2 days before and for 3 days after RSV inoculation. RSV was measured serially in nasal washes using several different viral assays. Intranasal ALN-RSV01 was well tolerated, exhibiting a safety profile similar to saline placebo. The proportion of culture-defined RSV infections was 71.4 and 44.2% in placebo and ALN-RSV01 recipients, respectively (P = 0.009), representing a 38% decrease in the number of infected and a 95% increase in the number of uninfected subjects. The acquisition of infection over time was significantly lower in ALN-RSV01 recipients (P = 0.007 and P = 0.03, viral culture and PCR, respectively). Multiple logistic regression analysis showed that the ALN-RSV01 antiviral effect was independent of other factors, including preexisting RSV antibody and intranasal proinflammatory cytokine concentrations. ALN-RSV01 has significant antiviral activity against human RSV infection, thus establishing a unique proof-of-concept for an RNAi therapeutic in humans and providing the basis for further evaluation in naturally infected children and adults.