gebhart/patrepeval huggingface dataset:
Needle optical coherence elastography for the measurement of microscale mechanical contrast deep within human breast tissues (2013)

Optical coherence elastography (OCE) is an emerging imaging technique that probes microscale mechanical contrast in tissues with the potential to differentiate healthy and malignant tissues. However, conventional OCE techniques are limited to imaging the first 1 to 2 mm of tissue in depth. We demonstrate, for the first time, OCE measurements deep within human tissues using needle OCE, extending the potential of OCE as a surgical guidance tool. We use needle OCE to detect tissue interfaces based on mechanical contrast in both normal and malignant breast tissues in freshly excised human mastectomy samples, as validated against histopathology. Further, we demonstrate the feasibility of in situ measurements >4 cm from the tissue surface using ultrasound guidance of the OCE needle probe. With further refinement, our method may potentially aid in accurate detection of the boundary of the tumor to help ensure full removal of all malignant tissues, which is critical to the success of breast-conserving surgery.
Practical lock-freedom (2021)

Mutual-exclusion locks are currently the most popular mechanism for interprocess synchronisation, largely due to their apparent simplicity and ease of implementation. In the parallel-computing environments that are increasingly commonplace in high-performance applications, this simplicity is deceptive: mutual exclusion does not scale well with large numbers of locks and many concurrent threads of execution. Highly-concurrent access to shared data demands a sophisticated ‘fine-grained’ locking strategy to avoid serialising non-conflicting operations. Such strategies are hard to design correctly and with good performance because they can harbour problems such as deadlock, priority inversion and convoying. Lock manipulations may also degrade the performance of cache-coherent multiprocessor systems by causing coherency conflicts and increased interconnect traffic, even when the lock protects read-only data. In looking for solutions to these problems, interest has developed in lock-free data structures. By eschewing mutual exclusion it is hoped that more efficient and robust systems can be built. Unfortunately the current reality is that most lock-free algorithms are complex, slow and impractical. In this dissertation I address these concerns by introducing and evaluating practical abstractions and data structures that facilitate the development of large-scale lock-free systems. Firstly, I present an implementation of two useful abstractions that make it easier to develop arbitrary lock-free data structures. Although these abstractions have been described in previous work, my designs are the first that can be practically implemented on current multiprocessor systems. Secondly, I present a suite of novel lock-free search structures. This is interesting not only because of the fundamental importance of searching in computer science and its wide use in real systems, but also because it demonstrates the implementation issues that arise when using the practical abstractions I have developed. Finally, I evaluate each of my designs and compare them with existing lock-based and lock-free alternatives. To ensure the strongest possible competition, several of the lock-based alternatives are significant improvements on the best-known solutions in the literature. These results demonstrate that it is possible to build useful data structures with all the perceived benefits of lock-freedom and with performance better than sophisticated lock-based designs. Furthermore, and contrary to popular belief, this work shows that existing hardware primitives are sufficient to build practical lock-free implementations of complex data structures.
Spinal Synaptic Enhancement with Acute Intermittent Hypoxia Improves Respiratory Function after Chronic Cervical Spinal Cord Injury (2005)

Respiratory insufficiency is the leading cause of death after high-cervical spinal cord injuries (SCIs). Although respiratory motor recovery can occur with time after injury, the magnitude of spontaneous recovery is limited. We hypothesized that partial respiratory motor recovery after chronic cervical SCI could be strengthened using a known stimulus for spinal synaptic enhancement, intermittent hypoxia. Phrenic motor output was recorded before and after intermittent hypoxia from anesthetized, vagotomized, and pump-ventilated control and C2 spinally hemisected rats at 2, 4, and 8 weeks after injury. Weak spontaneous phrenic motor recovery was present in all C2-injured rats via crossed spinal synaptic pathways that convey bulbospinal inspiratory premotor drive to phrenic motoneurons on the side of injury. Intermittent hypoxia augmented crossed spinal synaptic pathways [phrenic long-term facilitation; pLTF] for up to 60 min after hypoxia at 8 weeks, but not 2 weeks, after injury. Ketanserin, a serotonin 2A receptor antagonist, administered before intermittent hypoxia at 8 weeks after injury prevented pLTF. Serotonergic innervation near phrenic motoneurons was assessed after injury. The limited magnitude of pLTF at 2 weeks was associated with an injury-induced reduction in serotonin-containing nerve terminals in the vicinity of phrenic motoneurons ipsilateral to C2 hemisection. Thereafter, pLTF magnitude progressively increased with the recovery of serotonergic innervation in the phrenic motor nucleus. Intermittent hypoxia (or pLTF) has intriguing possibilities as a therapeutic tool, because its greatest efficacy may be in patients with chronic SCI, a time when most patients have already achieved maximal spontaneous functional recovery.
Brain Adenosine Receptors as Targets for Therapeutic Intervention in Neurodegenerative Diseases (1999)

Adenosine acts as a neurotransmitter in the brain through the activation of four specific G-protein-coupled receptors (the A1, A2A, A2B, and A3 receptors). The A1 receptor has long been known to mediate neuroprotection, mostly by blockade of Ca2+ influx, which results in inhibition of glutamate release and reduction of its excitatory effects at a postsynaptic level. However, the development of selective A1 receptor agonists as antiischemic agents has been hampered by their major cardiovascular side effects. More recently, apparently deleterious effects have been reported following the activation of other adenosine receptor subtypes, namely, the A2A and the A3 receptors. In particular, selective A2A receptor antagonists have been demonstrated to markedly reduce cell death associated with brain ischemia in the rat, suggesting that the cerebral A2A receptor may indeed contribute to the development of ischemic damage. The beneficial effects evoked by A2A antagonists may be due to blockade of presynaptic A2A receptors (which are stimulatory on glutamate release) and/or to inhibition of A2A receptor-mediated activation of microglial cells. Even more puzzling data have been reported for the A3 receptor subtype, which can indeed mediate both cell protection and cell death, simply depending upon the degree of receptor activation and/or specific pathophysiological conditions. In particular, a mild subthreshold activation of this receptor has been associated with a reinforcement of the cytoskeleton and reduction of spontaneous apoptosis, which may play a role in "ischemic preconditioning" of the brain, according to which a short ischemic period may protect the brain from a subsequent, sustained ischemic insult that would be lethal. In contrast, a robust and prolonged activation of the A3 receptor has been shown to trigger cell death by either necrosis or apoptosis. Such apparently opposing actions may be reconciled by hypothesizing that adenosine-mediated cell killing during ischemia may be aimed at isolating the most damaged areas to favor those parts of the brain that still retain a chance for functional recovery. In fact, both A3 receptor-mediated cell death and A2A receptor-mediated actions may be viewed as an attempt to selectively kill irreversibly damaged cells in the "core" ischemic area, in order to save space and energy for the surrounding live cells in the "pneumbra" area. Hence, the pharmacological modulation of the A2A and A3 receptors via selective ligands may represent a novel strategy in the therapeutic approach to pathologies characterized by acute or chronic neurodegenerative events.
Shuffling with the Illiac and PM2I SIMD Networks (1984)

Two SIMD single-stage interconnection networks which have been proposed and studied in the literature are the Illiac type and PM2I. The ability of the Illiac and PM2I networks to perform the shuffle data permutation in an SIMD machine with N processors is examined. Two algorithms for an SIMD or multiple-SIMD machine with the PM2I network to perform the shuffle are given. One algorithm is used in the event that the SIMD machine is of the same size (in terms of number of processors) as the shuffle to be emulated. The other algorithm is used when the shuffle to be performed is of smaller size than the given machine with the PM2I network. It is proven that both algorithms require only one more network transfer than the previously published lower bound (which is log <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> S for a shuffle on S elements). Using the PM2I algorithm as a basis, an algorithm for the Illiac to emulate the shuffle is given. Its performance is 2√N - 1 transfers which is only three transfers more than the previously published lower bound of 2√N - 4.
EFFECTS OF STRUCTURED LIPID CONTAINING OMEGA-3 AND MEDIUM CHAIN FATTY ACIDS ON SERUM LIPIDS AND IMMUNOLOGICAL VARIABLES IN MICE (1999)

Diets supplemented with enzymatically produced structured lipid (SL) containing n-3 polyunsaturated fatty acids (eicosapentaenoic and docosahexaenoic) and caprylic acid or soybean oil (16.7 g/100 g) were fed to 4 to 6 week old female mice for 21 days. The effect of the diets on serum lipids (HDL-cholesterol, LDL-cholesteol. total cholesterol, triacylglycerol) and glucose concentrations were determined. The concentration of total cholesterol (49%), LDL cholesterol (35.4%) and triacylglycerol (53.2%) were significantly lowered in SL-fed group. The body weight gain in mice fed the soybean oil diet (control group) was significantly (p<0.05) greater than that in mice fed the SL diet after 21 days. The proportion of total T-cells (Thy 1.2+), T helper cells (CD4+), and T cytotoxic-suppressor cells (CD8+) in spleen were not significantly different between the two dietary groups as determined by flow cytometry.
Clearance of Theiler's virus infection depends on the ability to generate a CD8+ T cell response against a single immunodominant viral peptide (2003)

Theiler's murine encephalomyelitis virus (TMEV) induces a chronic demyelinating disease in the central nervous system of susceptible mice. Resistance to persistent TMEV infection maps to he D locus of the major histocompatibility complex suggesting a prominent role of antiviral CTL in the protective immune response. Introduction of the D(b) gene into the FVB strain confers resistance to this otherwise susceptible mouse line. Infection of the FVB/D(b) mouse with TMEV provides a model where antiviral resistance is determined by a response elicited by a single class I molecule. Resistant mice of the H-2(b) haplotype mount a vigorous H-2D(b)-restricted immunodominant response to the VP2 capsid protein. To investigate the extent of the contribution of the immunodominant T cell population in resistance to TMEV, FVB/D(b) mice were depleted of VP2-specific CD8(+) T cells by peptide treatment prior to virus infection. Peptide-treated mice were not able to clear the virus and developed extensive demyelination. These findings demonstrate that the D(b)-restricted CD8(+) T cells specific for a single viral peptide can confer resistance to TMEV infection. Our ability to manipulate this cellular response provides a model for investigating the mechanisms mediating protection against virus infection by CD8(+) T cells.
Ensemble Learning Using Decorrelated Neural Networks (1996)

We describe a decorrelation network training method for improving the quality of regression learning in 'ensemble' neural networks NNs that are composed of linear combinations of individual NNs. In this method, individual networks are trained by backpropogation not only to reproduce a desired output, but also to have their errors linearly decorrelated with the other networks. Outputs from the individual networks are then linearly combined to produce the output of the ensemble network. We demonstrate the performances of decorrelated network training on learning the 'three-parity' logic function, a noisy sine function and a one-dimensional non-linear function, and compare the results with the ensemble networks composed of independently trained individual networks without decorrelation training . Empirical results show than when individual networks are forced to be decorrelated with one another the resulting ensemble NNs have lower mean squared errors than the ensemble networks having independently trained individual networks. This method is particularly applicable when there is insufficient data to train each individual network on disjoint subsets of training patterns.
CD14 and lipopolysaccharide binding protein expression in a rat model of alcoholic liver disease. (1998)

Lipopolysaccharide-binding protein (LBP) and CD14 play key intermediary roles in the activation of cells by endotoxin. As endotoxin has been postulated to participate in promoting pathological liver injury in alcoholic liver disease, we investigated the role of LBP and CD14 in alcoholic liver injury. Rats were fed intragastrically ethanol or dextrose and either medium-chain triglycerides, corn oil, or fish oil for 4 weeks. Kupffer cells, endothelial cells, and hepatocytes were isolated. LBP and CD14 mRNA levels were measured in liver and individual cell types. The highest levels of LBP and CD14 mRNA levels in the liver were found in the fish oil/ethanol group, which was also the group with the greatest degree of pathological injury and inflammation. CD14 mRNA levels were also significantly elevated in groups fed unsaturated fatty acids with dextrose. CD14 expression was localized to the Kupffer cells and LBP expression to the hepatocytes. Expression of CD14 mRNA was also found in nonmyeloid cells in the two experimental groups (fish oil/ethanol and corn oil/ethanol) that had liver necrosis and inflammation. Our results suggest that enhanced LBP and CD14 expression correlates with the presence of pathological liver injury in alcoholic liver injury. Furthermore, unsaturated fatty acids may prime cells to respond to endotoxin by enhancing CD14 expression.
Molecular characterization of novel trispecific ErbB-cMet-IGF1R antibodies and their antigen-binding properties (2012)

Therapeutic antibodies are well established drugs in diverse medical indications. Their success invigorates research on multi-specific antibodies in order to enhance drug efficacy by co-targeting of receptors and addressing key questions of emerging resistance mechanisms. Despite challenges in production, multi-specific antibodies are potentially more potent biologics for cancer therapy. However, so far only bispecific antibody formats have entered clinical phase testing. For future design of antibodies allowing even more targeting specificities, an understanding of the antigen-binding properties of such molecules is crucial. To this end, we have generated different IgG-like TriMAbs (trispecific, trivalent and tetravalent antibodies) directed against prominent cell surface antigens often deregulated in tumor biology. A combination of surface plasmon resonance and isothermal titration calorimetry techniques enables quantitative assessment of the antigen-binding properties of TriMAbs. We demonstrate that the kinetic profiles for the individual antigens are similar to the parental antibodies and all antigens can be bound simultaneously even in the presence of FcγRIIIa. Furthermore, cooperative binding of TriMAbs to their antigens was demonstrated. All antibodies are fully functional and inhibit receptor phosphorylation and cellular growth. TriMAbs are therefore ideal candidates for future applications in various therapeutic areas.
Longitudinal Evaluation of Prostate-Specific Antigen Levels in Men With and Without Prostate Disease (1992)

The most significant factor affecting serum PSA levels with age is the development of prostate disease. Rate of change in PSA levels may be a sensitive and specific early clinical marker for the development of prostate cancer.
RPR 106541, a novel, airways‐selective glucocorticoid: effects against antigen‐induced CD4+T lymphocyte accumulation and cytokine gene expression in the Brown Norway rat lung (1997)

1. The effects of a novel 17-thiosteroid, RPR 106541, were investigated in a rat model of allergic airway inflammation. 2. In sensitized Brown Norway rats, challenge with inhaled antigen (ovalbumin) caused an influx of eosinophils and neutrophils into the lung tissue and airway lumen. In the lung tissue there was also an accumulation of CD4+ T lymphocytes and increased expression of mRNA for interleukin-4 (IL-4) and IL-5, but not interferon-gamma (IFN-gamma). These findings are consistent with an eosinophilia orchestrated by activated Th2-type cells. 3. RPR 106541 (10-300 microg kg[-1]), administered by intratracheal instillation into the airways 24 h and 1 h before antigen challenge, dose-dependently inhibited cell influx into the airway lumen. RPR 106541 (100 microg kg[-1]) caused a significant (P<0.01) (98%) inhibition of eosinophil influx and a significant (P<0.01) (100%) inhibition of neutrophil influx. RPR 106541 was approximately 7 times and 4 times more potent than budesonide and fluticasone propionate, respectively. 4. When tested at a single dose (300 microg kg[-1]), RPR 106541 and fluticasone each caused a significant (P<0.01) (100%) inhibition of CD4+ T cell accumulation in lung tissue. Budesonide (300 microg kg[-1]) had no significant effect. RPR 106541 and fluticasone (300 microg kg[-1]), but not budesonide (300 microg kg[-1]), significantly (P<0.05) inhibited the expression within lung tissue of mRNA for IL-4. RPR 106541 (300 microg kg[-1]) also significantly (P<0.05) inhibited expression of mRNA for IL-5. 5. The high topical potency of RPR 106541 in this model, which mimics important aspects of airway inflammation in human allergic asthmatics, suggests that this glucocorticoid may be useful in the treatment of bronchial asthma.
Molecular cloning, functional expression, tissue distribution, and in situ hybridization of the renal sodium phosphate (Na + /P i ) transporter in the control and hypophosphatemic mouse (1994)

The current studies were designed to isolate a cDNA encoding the control mouse renal sodium phosphate (Na+/P(i)) transporter and to determine mRNA levels encoding this transporter in control and (Hyp) mice. A 2.4 kb cDNA was isolated from a control mouse kidney cDNA library using a PCR-amplified 850 base pair (bp) fragment of rat cDNA. The cDNA encoding the mouse renal Na+/P(i) transporter shows sequence similarity to the rat and human Na+/P(i) transporters. The predicted protein exhibits 98% and 91% amino acid sequence identity with the rat and human proteins, respectively. A cRNA was synthesized from the cDNA and showed an expression of sodium-dependent phosphate transport in Xenopus laevis oocytes. Northern blot analysis of renal poly(A)+ RNA from (Hyp) and control mice showed a threefold decrease in mRNA level in the (Hyp) mice compared with control mice. In situ hybridization analysis localizes the Na+/P(i) transporter message to the renal proximal tubule, with message levels distinctly lower in the (Hyp) mouse. Also, genomic Southern blotting suggests that the gene encoding the sodium phosphate transporter is structurally identical in the control and (Hyp) mice. These studies suggest that we have cloned the cDNA encoding the renal Na+/P(i) transporter in the control [C57BL/6J+/ymale] mouse, localized the message to the renal proximal tubule, and shown that the mRNA level encoding the renal Na+/P(i) transporter is decreased in the hypophosphatemic mouse.
Chemical Genetics: Drug Screens in Zebrafish (2005)

High throughput chemical genetic screens for compounds with specific biological activity in a whole organism are feasible using zebrafish embryos. At least two medium to large scale drug screens have been carried out to date, leading to the identification of compounds that disturb zebrafish development. Chemical genetics using zebrafish embryos may become an important step in the discovery of drugs and their targets.
Experimental study of NIR transmittance of the human skull (2006)

The results of measurements of transmittance of high power laser irradiation through skull bones and scalp are presented. Dependences of transmittance on sample thickness were received. Character of transmittance was investigated and characteristics of heterogeneity of the scattering structure of the skull bones are proposed. Besides that, variation of temperature of skull and scalp surfaces under exposure of high power laser irradiation during experiments was controlled. Experimental results were verified by Monte-Carlo simulations.
Re-evaluating gadolinium(III) texaphyrin as a radiosensitizing agent. (2000)

Gadolinium(III) texaphyrin (Gd-tex) was recently proposed as a radiosensitizing agent that combines preferential tumor uptake with detection of drug localization by magnetic resonance imaging (S. W. Young et al., Proc. Natl. Acad. Sci. USA, 93: 6610-6615, 1996). In view of the initial report on this compound, four radiobiology laboratories undertook independent efforts to further study radiosensitization by Gd-tex. In addition to repeating the previously reported studies on Gd-tex in HT-29 cells, we tested five other human tumor cell lines (U-87 MG, U251-NCI, SW480, A549, and MCF-7). These studies included a Gd-tex treatment period of 24 h before irradiation (as in the original publication), with concentrations of Gd-tex ranging from 20-500 microM. In neither the HT-29 cells nor any of the other five human cell lines did we see radiation sensitization by Gd-tex. Two cell lines (MCF-7 and U-87 MG) were further tested for radiosensitization by Gd-tex under hypoxic conditions. No radiosensitization was observed in either case. Finally, the radiation response of two tumor lines were assessed in vivo. Neither HT-29 xenografts in severe combined immunodeficient (SCID) mice nor RIF-1 tumors growing in C3H mice demonstrated radiosensitization after Gd-tex treatment before single or fractionated doses of radiation. Our results raise questions about the efficacy of Gd-tex as a radiosensitizing agent.
Hin Recombinase Bound to DNA: the Origin of Specificity in Major and Minor Groove Interactions (1994)

The structure of the 52-amino acid DNA-binding domain of the prokaryotic Hin recombinase, complexed with a DNA recombination half-site, has been solved by x-ray crystallography at 2.3 angstrom resolution. The Hin domain consists of a three-alpha-helix bundle, with the carboxyl-terminal helix inserted into the major groove of DNA, and two flanking extended polypeptide chains that contact bases in the minor groove. The overall structure displays features resembling both a prototypical bacterial helix-turn-helix and the eukaryotic homeodomain, and in many respects is an intermediate between these two DNA-binding motifs. In addition, a new structural motif is seen: the six-amino acid carboxyl-terminal peptide of the Hin domain runs along the minor groove at the edge of the recombination site, with the peptide backbone facing the floor of the groove and side chains extending away toward the exterior. The x-ray structure provides an almost complete explanation for DNA mutant binding studies in the Hin system and for DNA specificity observed in the Hin-related family of DNA invertases.