gebhart/patrepeval huggingface dataset:
EXT 1 Gene Mutation Induces Chondrocyte Cytoskeletal Abnormalities and Defective Collagen Expression in the Exostoses (2000)

Hereditary multiple exostoses (HME), an autosomal skeletal disorder characterized by cartilage-capped excrescences, has been ascribed to mutations in EXT 1 and EXT 2, two tumor suppressor-related genes encoding glycosyltransferases involved in the heparan sulfate proteoglycan (HSPG) biosynthesis. Taking advantage of the availability of three different exostoses from a patient with HME harboring a premature termination codon in the EXT 1 gene, morphological, immunologic, and biochemical analyses of the samples were carried out. The cartilaginous exostosis, when compared with control cartilage, exhibited alterations in the distribution and morphology of chondrocytes with abundant bundles of actin filaments indicative of cytoskeletal defects. Chondrocytes in the exostosis were surrounded by an extracellular matrix containing abnormally high amounts of collagen type X. The unexpected presence of collagen type I unevenly distributed in the cartilage matrix further suggested that some of the hypertrophic chondrocytes detected in the cartilaginous caps of the exostoses underwent accelerated differentiation. The two mineralized exostoses presented lamellar bone arrangement undergoing intense remodeling as evidenced by the presence of numerous reversal lines. The increased electrophoretic mobility of chondroitin sulfate and dermatan sulfate proteoglycans (PGs) extracted from the two bony exostoses was ascribed to an absence of the decorin core protein. Altogether, these data indicate that EXT mutations might induce a defective endochondral ossification process in exostoses by altering actin distribution and chondrocyte differentiation and by promoting primary calcification through decorin removal.
Advances in the diagnosis and management of keratoconjunctivitis sicca (1998)

Keratoconjunctivitis sicca is a common ocular surface disease that develops in patients with aqueous tear deficiency. Recent advances have been made in diagnosis, pathogenesis, and therapy of this condition. Advances in diagnosis include improved understanding of the specificity of the tests used for diagnosis, elucidation of the mechanism of the ocular surface rose bengal and fluorescein staining that occurs in this condition, and the expanded use of impression cytology. Advances in pathogenesis include the concept that keratoconjunctivitis sicca is a condition of abnormal growth and differentiation and immune activation of the ocular surface epithelium. These findings indicate that keratoconjunctivitis sicca may represent a chronic wound-healing response to a poorly lubricated and inflamed ocular surface. Advances in therapy include improved nonpreserved artificial tears and therapies targeted at decreasing ocular surface inflammation.
340. Development of a Nuclease Screen to Improve Cas9 Targeting Specificity (2015)

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) bacterial immunity targets invading nucleic acid sequences using an RNA guide (gRNA). The well-defined Cas9 from Streptococcus pyogenes’ type II CRISPR system has been utilized as a gene editing tool in a vast assortment of organisms. However, an inherent lack of specificity limits the potential of the current system and presents challenges to interpreting experimental results. A plasmid cleavage based screening platform has been developed with the intent to increase the fidelity of the Cas9 system. Utilizing both positive and negative selection, the screen can be used to identify variants of Cas9 or its gRNA with improved specificity. Positive selection of variants with activity towards the appropriate target site proceeds through the removal of a plasmid containing an inducible suicide gene. Conversely, negative selection of variants with reduced activity on off-target substrates involves the retention of a plasmid with an antibiotic resistance gene. Preliminary results suggest that a gRNA with an insertion in the scaffold region of the RNA can decrease the level of off-target cleavage. These results suggest that the screening platform has the potential to identify novel protein or RNA variants with greater targeting specificity compared to the naturally occurring components. A Cas9 system with enhanced fidelity will expand the potential applications of the technology and accelerate its ability to interrogate biological systems.
Towards the Rational Design of Magnetic Resonance Imaging Contrast Agents: Isolation of the Two Coordination Isomers of Lanthanide DOTA‐Type Complexes (2003)

Controlling water exchange: Square antiprism (SAP; left) and twisted square antiprism (TSAP; right) coordination isomers of LnIIIDOTA-type complexes (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) may be isolated by choosing substituents on the ring and arms with identical chirality for the TSAP isomer, or with opposite chirality for the SAP isomer. The water exchange rates of the complexes differ by an order of magnitude.
Expression and clinical significance of multidrug resistance proteins in brain tumors (2010)

Chemotherapeutics drugs are interrupted in the end-feet of neuroepithelial cells of the BBB by P-gp, which weakens the chemotherapeutic effect. P-gp marks the BBB, and the transporter is localized in the luminal endothelial compartment where it co-localizes with caveolin-1.
Role of calpain in hydrogen peroxide induced cataract (1993)

The purpose of these experiments was to examine the relationship between oxidation cataract and proteolysis in cultured rat lens. Hydrogen peroxide cataract showed insolubilization of protein, loss of 31 kDa beta B1-crystallin polypeptide, decreases in soluble calpain, and increases in insoluble calpain. This suggested that calpain may be activated in hydrogen peroxide treated lenses, since beta B1 is a known calpain substrate, and calpain undergoes autolysis and degradation when activated. Furthermore, the cysteine protease inhibitor E64 was partially effective in preventing development of H2O2-cataract. E64 also prevented the loss of the 31 kDa beta B1-crystallin polypeptide and decreased the loss of calpain in the lens. These results suggested that development of hydrogen peroxide induced cataract in rat lenses was associated with activation of calpain.
Impact of HIV Type 1 Protease, Reverse Transcriptase, Cleavage Site, and p6 Mutations on the Virological Response to Quadruple Therapy with Saquinavir, Ritonavir, and Two Nucleoside Analogs (2001)

Genotype alterations of HIV-1 protease, reverse transcriptase, cleavage sites p7/p1 and p1/p6, as well as p6(gag) and transframe protein p6* were studied in an observational cohort of 42 individuals who received antiretroviral therapy consisting of saquinavir, ritonavir, and two nucleoside analogs. In a multivariate logistic regression analysis, the prior protease inhibitor experience (odds ratio, 6.20; 95% CI, 1.22-31.38) and the presence of primary protease mutations (odds ratio, 9.99; 95% CI, 1.05-94.72) were independently associated with virological failure. Moreover, a trend was observed in that individuals with N-terminal amino acid insertions in the proline-rich motif of the p6(gag) protein were less likely to experience virological failure (OR, 0.17; 95% CI, 0.02-1.35; p = 0.09). In contrast, the presence of secondary protease, reverse transcriptase, or cleavage site mutations was not independently associated with treatment failure. However, mutations at cleavage site p7/p1 (p = 0.01) and C-terminal p6* mutations (p = 0.02) were both associated with primary protease mutations. In conclusion, the presence of primary protease mutations was the most important predictor of the subsequent virological response. Moreover, there is some evidence that insertions in the proline-rich area of the p6(gag) protein may affect the virological response. The relationship between mutations of cleavage sites or C-terminal p6* residues and protease mutations suggests that these alterations may serve a compensatory role, increasing viral fitness.
Non-viral vectors in cancer gene therapy: principles and progress (2001)

This review focuses on the use of synthetic (non-viral) delivery systems for cancer gene therapy. Therapeutic strategies such as gene replacement/mutation correction, immune modulation and molecular therapy/'suicide' gene therapy type approaches potentially offer unique and novel ways of fighting cancer, some of which have already shown promise in early clinical trials. However, the specific and efficient delivery of the genetic material to remote tumors/metastases remains a challenge, which is being addressed using a variety of viral and non-viral systems. Each of these disparate systems has distinct advantages and disadvantages, which need to be taken into account when a specific therapeutic gene is being used. The review concentrates on particulate gene delivery systems, which are formed through non-covalent complexation of cationic carrier molecules (e.g. lipids or polymers) and the negatively charged plasmid DNA. Such systems tend to be comparatively less efficient than viral systems, but have the inherent advantage of flexibility and safety. The DNA-carrier complex acts as a protective package, and needs to be inert and stable while in circulation. Once the remote site has been reached the complex needs to efficiently transfect the targeted (tumor) cells. In order to improve overall transfection specificity and efficiency it is necessary to optimize intracellular trafficking of the DNA complex as well as the performance after systemic administration. Common principles and specific advantages or disadvantages of the individual synthetic gene delivery systems are discussed, and their interaction with tumor-specific and generic biological barriers are examined in order to identify potential strategies to overcome them.
Ipsilon's General Switch Management Protocol Specification Version 2.0 (1998)

The General Switch Management Protocol (GSMP), is a general purpose protocol to control an ATM switch. GSMP allows a controller to establish and release connections across the switch; add and delete leaves on a point-to-multipoint connection; manage switch ports; request configuration information; and request statistics.
Multiple Organ Failure, Multiple Organ Dysfunction Syndrome, and Systemic Inflammatory Response Syndrome (1997)

The concept of multiple organ failure and related abnormalities was first developed in the 1970s. Multiple organ failure became evident when the support systems in intensive care units were able to keep patients alive long enough for multiple organ problems to develop in them. The high mortality of patients with multiple organ failure provided a focus for the problems that ultimately led to death for many patients in the intensive care unit. The frequency of infection, sepsis, or inflammation in producing multiple organ failure led to clinical trials of so-called magic bullets for the treatment of patients with sepsis. These trials have had either limited success or negative results, despite considerable evidence for efficacy or protection by such agents in experimental animals and in studies of normal human volunteers. I believe a major reason for these negative results has been the use of general entry criteria for the trials rather than the treatment of specific diseases or injuries.
First Computational Evidence for a Catalytic Bridging Hydroxide Ion in a Phosphodiesterase Active Site (2001)

Phosphodiesterases are clinical targets for a variety of biological disorders, because this superfamily of enzymes regulates the intracellular concentration of cyclic nucleotides that serve as the second messengers playing a critical role in a variety of physiological processes. Understanding the structure and mechanism of a phosphodiesterase will provide a solid basis for rational design of the more efficient therapeutics. Although a three-dimensional X-ray crystal structure of the catalytic domain of human phosphodiesterase 4B2B was recently reported, it is uncertain whether a critical bridging ligand in the active site is a water molecule or a hydroxide ion. The identity of this bridging ligand is theoretically determined by performing first-principles quantum chemical calculations on models of the active site. All the results obtained indicate that this critical bridging ligand in the active site of the reported X-ray crystal structure is a hydroxide ion, rather than a water molecule, expected to serve as the nucleophile to initialize the catalytic degradation of the intracellular second messengers.
Oxidative effects of heme and porphyrins on proteins and lipids. (1989)

Heme and porphyrins catalyze the formation of various reactive oxygen species under widely different conditions. Porphyrins are potent photosensitizers capable of transferring the energy of their excited state to oxygen, forming 1O2. Heme, by virtue of its iron content, is not a photosensitizer, but it can react with H2O2 forming reactive oxygen intermediates whose nature depends on the oxidation state of the iron. Ferric heme gives rise to a porphyrin cation radical, while ferrous heme catalyzes the formation of OH.. The reactive species formed by heme and porphyrins oxidize susceptible functional groups on protein and lipid components of membranes as well as serum and cytosolic proteins. Oxidation of membrane-bound proteins occurs independently of lipid peroxidation and it is characterized by extensive cross-linking, which takes place subsequent to amino acid oxidation. Serum and cytosolic proteins that bind and may transport heme and porphyrins are of special interest since they can modulate their toxicity by affecting their availability and reactivity. In addition, these proteins are particularly susceptible to oxidation, especially by heme, due to their proximity to the oxidizing species that are formed.
Malaria Parasites Adopt Host Cell Superoxide Dismutase (1983)

Aerobic organisms depend on superoxide dismutase to suppress the formation of dangerous species of activated oxygen. Intraerythrocytic stages of the malaria parasite exist within a highly aerobic environment and cause the generation of increased amounts of activated oxygen. Plasmodium berghei in mice was found to derive a substantial amount of superoxide dismutase activity from the host cell cytoplasm. Plasmodia isolated from mouse red cells contained mouse superoxide dismutase, whereas rat-derived parasites contained the rat enzyme. This is believed to be the first example of the acquisition of a host cell enzyme by an intracellular parasite.
Entrainment and stimulated emission of ultrasonic piezoelectric auto-oscillators (2007)

Theoretical modeling and laboratory tests are conducted for nonlinear auto-oscillating piezoelectric ultrasonic devices coupled to reverberant elastic bodies. The devices are shown to exhibit behavior familiar from the theory of coupled auto-oscillators. In particular, these spontaneously emitting devices adjust their limit-cycle frequency to the spectrum of the body. It is further shown that the auto-oscillations can be entrained by an applied field; an incident wave at a frequency close to the frequency of the natural limit cycle entrains the oscillator. Special attention is paid to the phase of entrainment. Depending on details, the phase is such that the oscillator can be in a state of stimulated emission: the incident field amplifies the ultrasonic power emitted by the oscillator. These behaviors are essential to eventual design of an ultrasonic system that would consist of a number of such devices all synchronized to their mutual field, a system that would be an analog to a laser. A prototype uaser is constructed.
Cardiac reperfusion injury: Aging, lipid peroxidation, and mitochondrial dysfunction (1998)

Cardiac reperfusion and aging are associated with increased rates of mitochondrial free radical production. Mitochondria are therefore a likely site of reperfusion-induced oxidative damage, the severity of which may increase with age. 4-Hydroxy-2-nonenal (HNE), a major product of lipid peroxidation, increases in concentration upon reperfusion of ischemic cardiac tissue, can react with and inactivate enzymes, and inhibits mitochondrial respiration in vitro. HNE modification of mitochondrial protein(s) might, therefore, be expected to occur during reperfusion and result in loss in mitochondrial function. In addition, this process may be more prevalent in aged animals. To begin to test this hypothesis, hearts from 8- and 24-month-old rats were perfused in Langendorff fashion and subjected to periods of ischemia and/or reperfusion. The rate of state 3 respiration of mitochondria isolated from hearts exposed to ischemia (25 min) was approximately 25% less than that of controls, independent of age. Reperfusion (40 min) caused a further decline in the rate of state 3 respiration in hearts isolated from 24- but not 8-month-old rats. Furthermore, HNE modification of mitochondrial protein (approximately 30 and 44 kDa) occurred only during reperfusion of hearts from 24-month-old rats. Thus, HNE-modified protein was present in only those mitochondria exhibiting reperfusion-induced declines in function. These studies therefore identify mitochondria as a subcellular target of reperfusion damage and a site of age-related increases in susceptibility to injury.
The relationship between the WISC-R and WRAT-R for a sample of rural referred children (1986)

WISC-R Verbal and Performance IQ scores obtained from a sample of 124 referred children were correlated with WRAT-R achievement scores. The Verbal IQ was found to predict Reading, Spelling, and Arithmetic. The Performance IQ did not add significantly to the predictions. The results were consistent with earlier studies that examined the relationship of the WISC-R to the WRAT.
Microfluidic chip for high efficiency DNA extraction (2004)

A high efficiency DNA extraction microchip was designed to extract DNA from lysed cells using immobilized beads and the solution flowing back and forth. This chip was able to increase the extraction efficiency by 2-fold when there was no serum. When serum existed in the solution, the extraction efficiency of immobilized beads was 88-fold higher than that of free beads. The extraction efficiency of the microchip was tested under different conditions and numbers of E. coli cells. When the number of E. coli cells was between 10(6) and 10(8) in 25 microl of whole blood, the extraction efficiency using immobilized beads was only slightly higher than that using free beads (10(0) to 10(1) fold). When the number of E. coli cells was in the range 10(4) to 10(6) in 25 microl of whole blood, the extraction efficiency of immobilized beads was greater than that of the free beads (10(1) to 10(2) fold). When the number of E. coli cells was lower, in the range 10(3) to 10(4) in 25 microl of whole blood, the extraction efficiency of immobilized beads was much higher than that of the free beads (10(2) to 10(3) fold). This study indicated that DNA could be efficiently extracted even when the number of bacterial cells was smaller (10(5) to 10(3)). This microfluidic extraction chip could find potential applications in rare sample genomic study.
A carotenogenic gene cluster exists on a large plasmid in Thermus thermophilus (1994)

In Thermus thermophilus HB27, the crtB gene encoding phytoene synthase was found to exist on the large plasmid, pTT27. One of the carotenoid under-producing mutants, Crt31, carried a derivative of pTT27 (pTT27') in which deletion and inversion were observed near the crtB gene. T. thermophilus HB8 also contained a large plasmid which showed homology to pTT27 and the crtB gene. These results suggested that genes for carotenoid biosynthesis occurred as a cluster on a large plasmid in Thermus thermophilus. This is the first report to show directly that carotenogenesis is plasmid-encoded in microorganisms.
Blinkering Surveillance: Enabling Video Privacy through Computer Vision (2003)

In this paper we describe a technology for protecting privacy in video systems. The paper presents a review of privacy in video surveillance and describes how a computer vision approach to understanding the video can be used to represent “just enough ” of the information contained in a video stream to allow video-based tasks (including both surveillance and other “person aware ” applications) to be accomplished, while hiding superfluous details, particularly identity, that can contain privacyintrusive information. The technology has been implemented in the form of a privacy console that manages operator access to different versions of the video-derived data according to access control lists. We have also built PrivacyCam—a smart camera that produces a video stream with the privacy-intrusive information already removed. 1
Managing and exploiting stress in the antibody factory (2007)

Like us, our cells have evolved strategies to cope with, and sometimes utilize, stress. Molecular analyses of plasma cell biogenesis, lifestyle and death suggest that protein synthesis-dependent stress is utilised to integrate differentiation, function and lifespan control. Plasma cells are short-lived professional secretory cells, each of them capable of releasing several thousands antibodies per second. Their differentiation from B lymphocytes entails the spectacular enlargement of the endoplasmic reticulum (ER), finalized to sustain massive Ig production. Nonetheless, symptoms of ER stress are evident, and the UPR-related transcription factor XBP-1 is essential for differentiation. Surprisingly, the development of such an efficient factory is matched by a decrease in proteasomes. The unbalanced load/capacity ratio leads to accumulation of polyubiquitinated molecules and predisposes plasma cells to apoptosis. Exuberant antibody secretion imposes considerable stress on metabolic and redox homeostasis. Collectively, these stressful conditions may link plasma cell death to antibody production, providing a molecular counter for secreted molecules, as well as an explanation for the peculiar sensitivity of myeloma cells towards proteasome inhibitors.
Adeno-associated viral transfer of opioid receptor gene to primary sensory neurons: A strategy to increase opioid antinociception (2003)

To develop a genetic approach for the treatment of pain, we introduced a recombinant adeno-associated viral (rAAV) vector containing the cDNA for the mu-opioid receptor (muOR) into primary afferent neurons in dorsal root ganglia (DRGs) of rats, which resulted in a long-lasting (>6 months) increase in muOR expression in DRG neurons. The increase greatly potentiated the antinociceptive effects of morphine in rAAV-muOR-infected rats with and without inflammation. Perforated patch recordings indicated that the efficacy and potency of opioid inhibition of voltage-dependent Ca(2+) channels were enhanced in infected neurons, which may underlie the increase in opiate efficacy. These data suggest that transfer of opioid receptor genes into DRG cells with rAAV vectors may offer a new therapeutic strategy for pain management.