gebhart/patrepeval huggingface dataset:
Synthesis of Pyrazolo[3,4-b]pyridines and Pyrido[2,3-d]pyrimidinones by Hetero-Diels-Alder Reaction of Pyrazolyl- and Pyrimidinilimines under Microwave Irradiation in Dry Media (2000)

Article Synthesis of Pyrazolo[3,4-b]pyridines and Pyrido[2,3-d]pyrimidinones by Hetero-Diels-Alder Reaction of Pyrazolyl- and Pyrimidinilimines under Microwave Irradiation in Dry Media was published on August 1, 2000 in the journal Heterocyclic Communications (volume 6, issue 4).
Delayed Nerve Stimulation Promotes Axon-Protective Neurofilament Phosphorylation, Accelerates Immune Cell Clearance and Enhances Remyelination In Vivo in Focally Demyelinated Nerves (2014)

Rapid and efficient axon remyelination aids in restoring strong electrochemical communication with end organs and in preventing axonal degeneration often observed in demyelinating neuropathies. The signals from axons that can trigger more effective remyelination in vivo are still being elucidated. Here we report the remarkable effect of delayed brief electrical nerve stimulation (ES; 1 hour @ 20 Hz 5 days post-demyelination) on ensuing reparative events in a focally demyelinated adult rat peripheral nerve. ES impacted many parameters underlying successful remyelination. It effected increased neurofilament expression and phosphorylation, both implicated in axon protection. ES increased expression of myelin basic protein (MBP) and promoted node of Ranvier re-organization, both of which coincided with the early reappearance of remyelinated axons, effects not observed at the same time points in non-stimulated demyelinated nerves. The improved ES-associated remyelination was accompanied by enhanced clearance of ED-1 positive macrophages and attenuation of glial fibrillary acidic protein expression in accompanying Schwann cells, suggesting a more rapid clearance of myelin debris and return of Schwann cells to a nonreactive myelinating state. These benefits of ES correlated with increased levels of brain derived neurotrophic factor (BDNF) in the acute demyelination zone, a key molecule in the initiation of the myelination program. In conclusion, the tremendous impact of delayed brief nerve stimulation on enhancement of the innate capacity of a focally demyelinated nerve to successfully remyelinate identifies manipulation of this axis as a novel therapeutic target for demyelinating pathologies.
Molecular Biology of Bacteriophage T4 (1994)

Molecular Biology of Bacteriophage T4 has been the authoritative volume about T4 phage, a model organism instrumental in numerous interdisciplinary scientific discoveries from the 1940s to the present. This book, originally published by ASM Press in 1994, represents a time-tested resource on all aspects of T4, including DNA metabolism, regulation of gene expression, phage morphogenesis, structure-function relationships of phage proteins, host-phage interactions, experiments in T4 genetics, and detailed research protocols. This landmark compendium has historical and educational value for microbiology students, early career researchers, and senior investigators alike. Since T4 has played a central role in the development of molecular biology as an academic discipline, the themes and experiments presented in this book provide an excellent framework for the design of graduate and undergraduate courses in prokaryotic genetics and biochemistry and provides a wealth of resources for those investigating biology and mechanisms of the numerous recently discovered phages.
Projection of Diabetes Burden Through 2050 (2001)

If recent trends in diabetes prevalence rates continue linearly over the next 50 years, future changes in the size and demographic characteristics of the U.S. population will lead to dramatic increases in the number of Americans with diagnosed diabetes.
Localization of mRNAs by in‐situ hybridization to the residual body at stages IX‐X of the cycle of the rat seminiferous epithelium: fact or artefact? (1994)

Several recent articles have reported localization of specific mRNAs in the rat testis to stage IX and X seminiferous tubules using in-situ hybridization. In all cases the expression was located basally in the tubules and appeared as discrete round clusters of grains close to the lamina propria. The localization was interpreted as being in Sertoli cells or leptotene spermatocytes. In this study we demonstrate that this pattern is most probably due to artefactual binding of probes to the residual body (RB). In the present study testicular tissue, perfusion-fixed with Bouin's and embedded in paraffin, was used, as this resulted in excellent morphological preservation such that RBs within tubules at stages VIII-X were clearly distinguishable. RNA content of the RBs was demonstrated at stages VIII-X using methyl green pyronin staining, and could be eliminated by pretreatment with RNAse or trichloroacetic acid. Localization of mRNAs for 11 seminiferous tubule proteins was assessed using 35S-labelled and digoxigenin-labelled riboprobes (activin receptor-II, alpha-inhibin, transferrin, androgen-binding protein (ABP), cyclic protein-2 (CP-2), CREM, sulphated glycoproteins 1 and 2 (SGP-1 and SGP-2), transition protein 2 (TP-2) and cystatin-C), and digoxigenin-labelled oligonucleotide probes (transition protein-1 (TP-1), TP-2 and protamine-1). All of these probes showed localization to the correct cell type(s) within the seminiferous epithelium. In addition, six antisense riboprobes (activin receptor-II, CREM, SGP-2, CP-2, cystatin C and alpha-inhibin) showed hybridization to basally located residual bodies in tubules at stages IX-X on one or more occasions, whereas residual bodies around the edge of the lumen (stage VIII) or in transit through the seminiferous epithelium showed no hybridization; sense probes showed no localization to residual bodies. A common feature of the probes which localized to the basal RBs was that they had been prepared using cDNA cloned into Bluescript SK- vector such that the antisense strand was generated from the T7 polymerase promotor. A cRNA prepared using T7 polymerase and Bluescript vector alone and a GC-rich 27mer oligonucleotide corresponding to the region of the multiple cloning site of Bluescript adjacent to the T7 site both localized uniquely to basal RB. It is concluded that the hybridization seen within RBs is probably a subtle artefact unique to RBs undergoing dissolution following fusion with Sertoli cell lysosomes, and may reflect nonspecific hybridization to GC-rich fragments of RNA.
The substrate-binding protein in bacterial ABC transporters: dissecting roles in the evolution of substrate specificity (2015)

ATP-binding cassette (ABC) transporters, although being ubiquitous in biology, often feature a subunit that is limited primarily to bacteria and archaea. This subunit, the substrate-binding protein (SBP), is a key determinant of the substrate specificity and high affinity of ABC uptake systems in these organisms. Most prokaryotes have many SBP-dependent ABC transporters that recognize a broad range of ligands from metal ions to amino acids, sugars and peptides. Herein, we review the structure and function of a number of more unusual SBPs, including an ABC transporter involved in the transport of rare furanose forms of sugars and an SBP that has evolved to specifically recognize the bacterial cell wall-derived murein tripeptide (Mtp). Both these examples illustrate that subtle changes in binding-site architecture, including changes in side chains not directly involved in ligand co-ordination, can result in significant alteration of substrate range in novel and unpredictable ways.
Fibre-optic sensor based on surface plasmon resonance (1996)

An optical fibre sensor based on resonant coupling between a mode of a monomode optical fibre and a surface plasmon is reported. It is demonstrated that, by measuring the optical power transmitted through the sensing element, very small changes in the refractive index of the sensed medium can be determined.
ACTIVITY AND PHYSICOCHEMICAL PROPERTIES OF PHOTOFRIN® (1991)

Upon certain conditions of storage, Photofrin samples changed their photodynamic therapy activity in mice. These samples showed similar absorption and high performance liquid chromatography (HPLC) profiles. The Photofrin samples that were active, however, had higher relative fluorescence yields than those which failed. Active and inactive samples also had different characteristics when analyzed by gel filtration chromatography using Sephacryl S-300; the failed samples had 60% or more high-molecular-weight fraction. The change of the amount of this high-molecular-weight fraction with the time of storage at room temperature could be clearly demonstrated. Results from fluorescence, HPLC and mass spectrometry studies suggest that the high-molecular-weight fraction may form by dehydration from or condensation between various components of Photofrin.
Dose-Dependent Effects of Theta Burst rTMS on Cortical Excitability and Resting-State Connectivity of the Human Motor System (2014)

Theta burst stimulation (TBS), a specific protocol of repetitive transcranial magnetic stimulation (rTMS), induces changes in cortical excitability that last beyond stimulation. TBS-induced aftereffects, however, vary between subjects, and the mechanisms underlying these aftereffects to date remain poorly understood. Therefore, the purpose of this study was to investigate whether increasing the number of pulses of intermittent TBS (iTBS) (1) increases cortical excitability as measured by motor-evoked potentials (MEPs) and (2) alters functional connectivity measured using resting-state fMRI, in a dose-dependent manner. Sixteen healthy, human subjects received three serially applied iTBS blocks of 600 pulses over the primary motor cortex (M1 stimulation) and the parieto-occipital vertex (sham stimulation) to test for dose-dependent iTBS effects on cortical excitability and functional connectivity (four sessions in total). iTBS over M1 increased MEP amplitudes compared with sham stimulation after each stimulation block. Although the increase in MEP amplitudes did not differ between the first and second block of M1 stimulation, we observed a significant increase after three blocks (1800 pulses). Furthermore, iTBS enhanced resting-state functional connectivity between the stimulated M1 and premotor regions in both hemispheres. Functional connectivity between M1 and ipsilateral dorsal premotor cortex further increased dose-dependently after 1800 pulses of iTBS over M1. However, no correlation between changes in MEP amplitudes and functional connectivity was detected. In summary, our data show that increasing the number of iTBS stimulation blocks results in dose-dependent effects at the local level (cortical excitability) as well as at a systems level (functional connectivity) with a dose-dependent enhancement of dorsal premotor cortex-M1 connectivity.
Drugs targeted against protein kinases (2001)

Current treatments for cancer (surgery, radiation and chemotherapy) are successful for early stage localised disease but have severe side effects. New treatments are needed to increase the cure rate and life expectancy of patients. With the discovery of oncogenes, tumour suppressor genes and an understanding of their role in the development of the malignant disease, a new era of therapy has begun. Cancer is a manifestation of deregulated signalling pathways that mediate cell growth and programmed cell death. Protein kinases are essential elements in these signalling pathways. In the US, Novartis launched Gleevec (imantinib, STI-571) in May 2001 as the first anticancer drug whose mechanism of action is kinase inhibition. In Phase I trials, 23/24 patients with chronic myelogenous leukaemia (CML) had complete remissions and the drug is relatively non-toxic. Herceptin (trastuzumab) is a monoclonal antibody (mAb) against a member of the growth factor receptor family (HER-2/neu) that was launched in 1998 by Genentech for the treatment of breast cancer. Trastuzumab has an excellent antitumour profile, particularly when used in combination with doxorubicin and paclitaxol. These drugs are pioneering the treatment of cancer based on the molecular understanding of the disease. Numerous drugs that target growth factor receptors and their signalling pathways are in advanced clinical trials. Herein, antibodies against receptors and small molecule inhibitors of kinases in signalling pathways will be summarised. Inter-disciplinary preclinical studies have identified chemicals that target specific kinases. We believe that clinical studies of these agents will yield new anticancer agents that target specific diseases and that are less toxic than current agents.
Physiologic or pathologic hypertrophy (1983)

Physiologic hypertrophy occurs as the result of exercise conditioning and is characterized by normal or supranormal left ventricular (LV) contractile function and reversibility of structural alterations. Whether hypertrophy produced by chronic abnormal loading can be termed 'physiologic' is a matter of debate because in experimental pressure overload hypertrophy normal in vivo ventricular function may be associated with abnormal in vitro function of the papillary muscles. In patients with moderate LV hypertrophy from aortic valve disease (angiographic mass less than 180 g/m2) ejection fraction (EF) is preserved, but at similar levels of afterload, when mass exceeds 180 g/m2, EF is depressed. Comparison of LV function with myocardial structure (endomyocardial biopsies) has shown that in patients with compensated LV function and those with left heart failure (EF less than 57%, LVEDP greater than 20 mm Hg and/or cardiac index less than 2.5 l/min/m2) interstitial fibrosis (IF) was increased to a similar extent (16 and 18%; normal less than 5%), whereas muscle fiber diameter (MFD; normal less than or equal to 20 mu) was larger (P less than 0.05) in the patients with failure (30 mu) than in those with preserved function (27 mu). Moreover patients with depressed postoperative function had a larger (P less than 0.01) preoperative MFD (35 mu) than those with normal postoperative function (30 mu). Seventeen months after successful aortic valve replacement IF increased (P less than 0.02) and MFD decreased (P less than 0.001) but did not become normal regardless whether postoperative function was normal or depressed. Thus in secondary hypertrophy myocardial structure is pathologic even in the presence of normal LV function and depressed function appears likely to be related to excessive fiber hypertrophy rather than to IF. Massive fiber hypertrophy heralds an unfavorable postoperative LV function and fibrosis is irreversible after surgical correction of the abnormal load.
A Monoclonal Antibody 7G7/B6, Binds to an Epitope on the Human Interleukin-2 (IL-2) Receptor That is Distinct From That Recognized by IL-2 or Anti-Tac (1985)

Murine splenocytes immune to influenza virus-activated human T-cells were fused with SP2/0 cells, selected in chemically defined HAT media, and subcloned to yield a monoclonal antibody (MAb) termed 7G7/B6. 7G7/B6 binds to lectin- and antigen-activated T-cells, but not resting T-cells or B-lymphoblastoid lines from the same donor. 7G7/B6 immunoprecipitates a 50-55 kD band from cell surface iodinated PHA-activated T-cells or the T-cell leukemia line HUT 102B2, as shown on SDS-PAGE. Cross-clearing studies demonstrate that 7G7/B6 binds the same cell surface molecule(s) as anti-Tac, a MAb which has been shown previously to recognize the human receptor for IL-2. 35S-methionine pulse chase experiments in HUT 102B2 cells reveal that 7G7/B6 binds to an early (less than 30 min) 35-37 kD and late (greater than 4 h) 50 kD protein. Sequential immunoprecipitations demonstrate that these are identical to the molecules identified by anti-Tac under similar conditions. However, only anti-Tac coprecipitates a higher molecular band at 110 kD. 7G7/B6 and anti-Tac do not competitively inhibit the binding of each other to PHA-activated T-cells. Functional studies reveal that in contrast to anti-Tac, 7G7/B6 has almost no inhibitory effect in vitro on IL-2-driven proliferation of IL-2-dependent T-cell lines, or alloimmune cytotoxic T-cell generation (however, once generated, these cytotoxic T-cells were both 7G7/B6 and anti-Tac positive). Finally, IL-2 does not inhibit the binding of 7G7/B6 to activated T-cells under conditions which result in up to 75% inhibition of anti-Tac binding. Therefore, 7G7/B6 is another MAb recognizing the human IL-2 receptor, but binding to an epitope distinct from that recognized by either IL-2 or anti-Tac.
Nitrite Infusion in Humans and Nonhuman Primates (2007)

We propose that nitrite functions as a physiological regulator of vascular function and endocrine nitric oxide homeostasis and suggest that it is an active metabolite of the organic nitrates that can be used therapeutically to bypass enzymatic tolerance.
Adaptive Control of Extreme-scale Stream Processing Systems (2006)

Distributed stream processing systems offer a highly scalable and dynamically configurable platform for time-critical applications ranging from real-time, exploratory data mining to high performance transaction processing. Resource management for distributed stream processing systems is complicated by a number of factors processing elements are constrained by their producer-consumer relationships, data and processing rates can be highly bursty, and traditional measures of effectiveness, such as utilization, can be misleading. In this paper, we propose a novel distributed, adaptive control algorithm that maximizes weighted throughput while ensuring stable operation in the face of highly bursty workloads. Our algorithm is designed to meet the challenges of extreme-scale stream processing systems, where overprovisioning is not an option, by making the best use of resources even when the proffered load is greater than available resources. We have implemented our algorithm in a real-world distributed stream processing system and a simulation environment. Our results show that our algorithm is not only self-stabilizing and robust to errors, but also outperforms traditional approaches over a broad range of buffer sizes, processing graphs, and burstiness types and levels.
High yield production of an inactivated coxsackie B3 adjuvant vaccine with protective effect against experimental myocarditis. (1993)

Dilated cardiomyopathy, perhaps chronic postviral fatigue syndrome as well as juvenile diabetes could be triggered by enteroviral infections. The frequency of sudden death after myocarditis and its relationship to enteroviral infections is disputed. Neonatal enteroviral disease is rare, but can be severe. It is also possible that enteroviruses pose a threat to immunocompromised patients, like bone marrow transplant recipients. Consequently, the emergence of chronic enteroviral diseases as a concept, prompted our attempts to produce an enteroviral vaccine. 1. Live attenuated enterovirus strains were previously in some cases shown to be suitable as vaccine candidates. We obtained neutralizing antibody titres ranging from 40-2560 against Coxsackie B3 virus (RD strain). Animals were protected to 90% against challenge infection. 2. Inactivated whole vaccine. We used beta-propiolactone to inactive Coxsackie B3 virus. 74% of the animals survived if the vaccine was prepared with Quil A matrix as adjuvant. The neutralisation antibody titres varied from < 5 to 320. By comparison aluminium hydroxide (p = 0.06) and Freund's adjuvant were inferior (p < 0.01). 3. Subunit vaccines. We have previously used the ISCOM (immunostimulatory complex) technology to produce a Coxsackie B3 subunit vaccine. High levels of neutralizing antibodies were obtained (512)-comparable to natural infection. All animals survived challenge infection after two booster doses with 16 nanogram of the ISCOM preparation. Limiting for this technique was the availability to include sufficient amount of antigenic protein material. In addition to neutralizing antibodies a cellular response might be obtainable. In conclusion we have shown that vaccine can be made against Coxsackie B3 virus with good protective effect and significant neutralisation antibody titre.(ABSTRACT TRUNCATED AT 250 WORDS)
Novel vitamin D analogs that modulate leukemic cell growth and differentiation with little effect on either intestinal calcium absorption or bone mobilization (1989)

Induction of terminal differentiation of leukemic and preleukemic cells is a therapeutic approach to leukemia and preleukemia. The 1 alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3], the hormonally active form of vitamin D3, can induce differentiation and inhibit proliferation of leukemia cells, but concentrations required to achieve these effects cause life-threatening hypercalcemia. Seven new analogs of 1,25(OH)2D3 were discovered to be either equivalent or more potent than 1,25(OH)2D3 as assessed by: (a) inhibition of clonal proliferation of HL-60, EM-2, U937, and patients' myeloid leukemic cells: and (b) induction of differentiation of HL-60 promyelocytes. Furthermore, these analogs stimulated clonal growth of normal human myeloid stem cells. The most potent analog, 1,25-dihydroxy-16ene-23yne-vitamin D3, was about fourfold more potent than 1,25(OH)2D3. This analog decreased clonal growth and expression of c-myc oncogene in HL-60 cells by 50% within ten hours of exposure. Effects on calcium metabolism of these novel analogs in vivo was assessed by intestinal calcium absorption (ICA) and bone calcium mobilization (BCM). Each of the analogs mediated markedly less (10 to 200-fold) ICA and BCM as compared with 1,25(OH)2D3. To gain insight into the possible mechanism of action of these new analogs, receptor binding studies were done with 1,25(OH)2-16ene-23yne-D3 and showed that it competed only about 60% as effectively as 1,25(OH)2D3 for 1,25(OH)2D3 receptors present in HL-60 cells and 98% as effective as 1,25(OH)2D3 for receptors present in chick intestinal cells. In summary, we have discovered seven novel vitamin D analogs that are more potent than the physiologic 1,25(OH)2D3 as measured by a variety of hematopoietic assays. In contrast, these compounds appear to have the potential to be markedly less toxic (induction of hypercalcemia). These novel vitamin D compounds may be superior to 1,25(OH)2D3 in a number of clinical situations including leukemia/preleukemia; they will provide a tool to dissect the mechanism of action of vitamin D seco-steroids in promoting cellular differentiation.