gebhart/patrepeval huggingface dataset:
Chiral Pyrrolo[2,3-d]pyrimidine and Pyrimido[4,5-b]indole Derivatives:  Structure−Activity Relationships of Potent, Highly Stereoselective A1-Adenosine Receptor Antagonists, (1996)

A series of 33 novel, mostly chiral pyrrolo[2,3-d]pyrimidine and pyrimido[4,5-b]indole derivatives has been synthesized and investigated in radioligand binding assays at the high-affinity adenosine receptor (AR) subtypes A1 and A2a. The compounds can be envisaged as adenine and hypoxanthine analogs lacking the nitrogen in the 7-position (7-deazaadenines and 7-deazahypoxanthines). 7-Deazaadenines were much more potent than 7-deazahypoxanthines at AR with A1AR affinities in the low-nanomolar range, extraordinarily high selectivity for the rat brain A1AR versus the A2aAR (several thousandfold), and high stereoselectivity (up to 96-fold). Pyrimido[4,5-b]indoles were more potent A1AR antagonists compared to pyrrolo[2,3-d]pyrimidines. Compound 34a (APEPI) is one of the most potent and most selective nonxanthine A1AR antagonists known to date (Ki = 2.8 nM, > 2000-fold A1-selective). A new class of very potent A1AR antagonists has been identified, namely, 2-phenyl-7-deazaadenines bearing a substituent at the exocyclic amino group (N4-substituted pyrrolo[2,3-d]pyrimidines). (R)-N- (1-Phenylethyl)-4-amino-5,6-dimethyl-2-phenyl-7H-pyrrolo[2,3-d]pyrimidin e (DPEAP, 17a) showed a Ki value of 6.7 nM at A1AR and > 4000-fold A1 selectivity. Different binding modes are postulated for the N4-substituted 4-aminopyrrolo[2,3-d]pyrimidines (e.g., 17a) and the 7-substituted derivatives (e.g., 1a), based on a comparison of steric, electronic, and hydrophobic properties of the two classes of compounds. Water solubility and lipophilicity have been determined for selected compounds. 4-Amino-5,6-dimethyl-2-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidine (4a) showed the highest water solubility/A1AR affinity ratio of 368 in the present series, over 2000-fold A1 selectivity, and 64-fold stereoselectivity (R > S). Therefore, 4a should be an interesting compound for in vivo evaluation.
Phosphorylation, ubiquitination and degradation of listeriolysin O in mammalian cells: role of the PEST-like sequence (2005)

Listeria monocytogenes is a bacterial pathogen that grows within the cytosol of infected host cells. Entry into the cytosol is largely mediated by a secreted bacterial cytolysin, listeriolysin O (LLO). In order to prevent host cell damage, the pore-forming activity of LLO is restricted to the phagosome. Compartmentalization of LLO requires a PEST-like sequence; PEST sequences can direct eukaryotic proteins for proteasomal degradation. Here we test the hypothesis that LLO's PEST-like sequence compartmentalizes pore-forming activity by targeting this bacterial protein for degradation in the host cytosol. We show that intracellular LLO was degraded in a proteasome-dependent manner, and that, prior to degradation, LLO was ubiquitinated and was phosphorylated within the PEST-like sequence. However, wild-type LLO and PEST region mutants had similarly short intracellular half-lives and both the wild-type and mutant proteins were stabilized by inhibitors of host proteasomes. Additionally, blocking host proteasomes did not cause toxicity in a wild-type infection, but enhanced the cytotoxicity of PEST region mutants. Together with the observation that PEST region mutants exhibit higher intracellular LLO levels than wild-type bacteria, these data suggest that LLO's PEST-like region does not mediate proteasomal degradation by the host, but controls LLO production in the cytosol.
Clinical applications of PD-1-based therapy: a focus on pembrolizumab (MK-3475) in the management of melanoma and other tumor types (2015)

Preclinical work has led to an increased understanding of the immunomodulatory mechanisms involved in the regulation of the antitumor response in a variety of tumor types. PD-1 (programmed death 1) appears to be a key checkpoint involved in immune suppression in the tumor microenvironment, even in diseases not previously thought to be sensitive to immune manipulation. More recently, the subsequent clinical development of PD-1-based therapy has resulted in a major breakthrough in the field of oncology. Pembrolizumab, a humanized highly selective IgG4 anti-PD-1 monoclonal antibody, was recently approved for the treatment of advanced melanoma based on promising early-phase clinical data. Encouraging results have also been seen in other malignancies, and PD-1-targeted therapies are likely to markedly change the treatment landscape. Future work will center on rationally designed combination strategies in order to potentiate the antitumor immune response and overcome mechanisms of resistance.
[Register of persons having occupational diseases caused by work with sources of ionizing radiation]. (2000)

The authors present methodic approaches to elaboration of a Special Register of individuals engaged into nuclear power industry and having occupational diseases caused by work with sources of ionizing radiation. The article deals with input and output documents, methods of input information control, technologic scheme of the Register functioning and stages of its pilot exploitation.
Dose De-escalation Chemoprevention Trial of -Difluoromethylornithine in Patients With Colon Polyps (1994)

If DFMO is also found to be effective in suppressing polyamine contents in other target tissues, it may be useful in preventing a wide range of human epithelial cancers, including those of the prostate and breast.
The leucine zipper domain of avian cMyc is required for transformation and autoregulation. (1990)

Small deletions of 7 to 48 amino acids have been generated in the leucine zipper domain of the avian cMyc protein and the mutant cMyc proteins expressed using an avian retroviral vector. Retrovirally encoded cMyc protein transforms primary chick embryo fibroblasts and leads to abnormal regulation of the endogenous c-myc gene. Deletion of the most C-terminal leucine of the zipper motif confers a partial phenotype affecting some but not all parameters of transformation. Complete loss of transforming activity results from deletion of further leucine residues, including one which is not part of the heptad repeat. In cMyc transformed cells endogenous c-myc mRNA is expressed at a low level and is abnormally refractory to induction by serum stimulation. In contrast, a non-transforming cMyc protein which lacks the zipper does not affect normal c-myc expression. These results demonstrate that the leucine zipper domain of avian cMyc is required for both transformation and autoregulation, and suggests that essential leucine residues within the motif may be spaced differently from those in the zippers of Fos and Jun.
Cloning and expression of Mycobacterium aurum carotenogenesis genes in Mycobacterium smegmatis (1992)

This report describes the first successful transfer and complete expression of clustered mycobacterial genes controlling a biosynthetic pathway (carotenogenesis) in a homologous system. A genomic library of pigmented Mycobacterium aurum A+ (yellow-orange) DNA was constructed in shuttle vector pHLD-69. The colourless mutant A11 and the brick-red mutant NgR9 derived from M. aurum A+ were electroporated with the plasmid library. Among the transformants, colonies different in colour from the recipient mutants were detected, and were cloned. One of the clones from the transformed A11 mutant had an yellow-orange phenotype, and was designated A11T; one of the clones from the NgR9 (brick-red) mutant had an yellow-orange phenotype and was designated NgR9T. The carotenoid pigments from the A11T and NgR9T clones were analyzed and in both the end product of carotenogenesis in M. aurum (leprotene) was detected. A11T and NgR9T harboured the same recombinant plasmid (pC1) containing a 11-kb M. aurum fragment. pC1 was used to transform the colourless Mycobacterium smegmatis MC2-155 strain. All the transformants were pigmented. A colony (MC2-T) was arbitrarily chosen and leprotene was detected. It was therefore concluded that M. aurum genes involved involved in carotenogenesis had been cloned, and were expressed not only in M. aurum mutants, but also in M. smegmatis.
Closed Loop Dynamic Bit Allocation for Excitation Parameters in Analysis-by-Synthesis Speech Codec (2007)

A method for dynamically allocating bits for the adaptive and fixed codebook of an analysis-by-synthesis speech codec is proposed. The bit allocation is based on the closed loop weighted mean squared error. The different bit allocations identify various codebook configurations used by the adaptive and fixed codebooks of the codec. Unlike open loop approaches where the decision on a codebook configuration is made once per frame, in the closed loop approach the decision on which codebook configuration should be used is made in each subframe. A variable length code is used for coding the codebook configuration. The factorial packing codebook is used as the fixed codebook. The technique is a part of 8.5 kbps mode of EVRC-WB speech coding standard.
Targeted Therapy of Cancer: New Prospects for Antibodies and Immunoconjugates (2006)

Immunotherapy of cancer has been explored for over a century, but it is only in the last decade that various antibody-based products have been introduced into the management of patients with diverse cancers. At present, this is one of the most active areas of clinical research, with eight therapeutic products already approved in oncology. Antibodies against tumor-associated markers have been a part of medical practice in immunohistology and in vitro immunoassays for several decades, have even been used as radioconjugates in diagnostic imaging, and are now becoming increasingly recognized as important biological agents for the detection and treatment of cancer. Molecular engineering has improved the prospects for such antibody-based therapeutics, resulting in different constructs and humanized/human antibodies that can be administered frequently. Consequently, a renewed interest in the development of antibodies conjugated with radionuclides, drugs, and toxins has emerged. We review how antibodies and immunoconjugates have influenced cancer detection and therapy, and also describe promising new developments and challenges for broader applications.
Hydroxylated Tropolones Inhibit Hepatitis B Virus Replication by Blocking Viral Ribonuclease H Activity (2014)

Hepatitis B virus (HBV) remains a major human pathogen despite the development of both antiviral drugs and a vaccine, in part because the current therapies do not suppress HBV replication far enough to eradicate the virus. Here, we screened 51 troponoid compounds for their ability to suppress HBV RNaseH activity and HBV replication based on the activities of α-hydroxytropolones against HIV RNaseH, with the goal of determining whether the tropolone pharmacophore may be a promising scaffold for anti-HBV drug development. Thirteen compounds inhibited HBV RNaseH, with the best 50% inhibitory concentration (IC50) being 2.3 μM. Similar inhibition patterns were observed against HBV genotype D and C RNaseHs, implying limited genotype specificity. Six of 10 compounds tested against HBV replication in culture suppressed replication via blocking of viral RNaseH activity, with the best 50% effective concentration (EC50) being 0.34 μM. Eighteen compounds inhibited recombinant human RNaseH1, and moderate cytotoxicity was observed for all compounds (50% cytotoxic concentration [CC50]=25 to 79 μM). Therapeutic indexes ranged from 3.8 to 94. Efficient inhibition required an intact α-hydroxytropolone moiety plus one or more short appendages on the tropolone ring, but a wide variety of constituents were permissible. These data indicate that troponoids and specifically α-hydroxytropolones are promising lead candidates for development as anti-HBV drugs, providing that toxicity can be minimized. Potential anti-RNaseH drugs are envisioned to be employed in combination with the existing nucleos(t)ide analogs to suppress HBV replication far enough to block genomic maintenance, with the goal of eradicating infection.
Latent semantic indexing (LSI) : TREC-3 report (1994)

This paper reports on recent developments of the Latent Semantic Indexing (LSI) retrieval method for TREC-3. LSI uses a reduced-dimension vector space to represent words and documents. An important aspect of this representation is that the association between terms is automatically captured, explicitly represented, and used to improve retrieval. We used LSI for both TREC-3 routing and adhoc tasks. For the routing tasks an LSI space was constructed using the training documents. We compared profiles constructed using just the topic words (no training) with profiles constructed using the average of relevant documents (no use of the topic words). Not surprisingly, the centroid of the relevant documents was 30% better than the topic words. This simple feedback method was quite good compared to the routing performance of other systems. Various combinations of information from the topic words and relevant documents provide small additional improvements in performance. For the adhoc task we c...
Improved electrochromic performance in inverse opal vanadium oxide films (2010)

Vanadium oxide inverse opal structures were fabricated by electrochemical deposition into self-assembled colloidal crystal templates and electrochromic performance was measured from the resulting macroporous vanadium oxide films. The periodic inverse opal structure resulted in an increased switching speed and a higher coloration contrast compared to similarly fabricated unstructured vanadium oxide films.
Computerized detection of masses in digital mammograms: Analysis of bilateral subtraction images (1991)

A computerized scheme is being developed for the detection of masses in digital mammograms. Based on the deviation from the normal architectural symmetry of the right and left breasts, a bilateral subtraction technique is used to enhance the conspicuity of possible masses. The scheme employs two pairs of conventional screen-film mammograms (the right and left mediolateral oblique views and craniocaudal views), which are digitized by a TV camera/Gould digitizer. The right and left breast images in each pair are aligned manually during digitization. A nonlinear bilateral subtraction technique that involves linking multiple subtracted images has been investigated and compared to a simple linear subtraction method. Various feature-extraction techniques are used to reduce false-positive detections resulting from the bilateral subtraction. The scheme has been evaluated using 46 pairs of clinical mammograms and was found to yield a 95% true-positive rate at an average of three false-positive detections per image. This preliminary study indicates that the scheme is potentially useful as an aid to radiologists in the interpretation of screening mammograms.
Tunable lenses using transparent dielectric elastomer actuators (2013)

Focus tunable, adaptive lenses provide several advantages over traditional lens assemblies in terms of compactness, cost, efficiency, and flexibility. To further improve the simplicity and compact nature of adaptive lenses, we present an elastomer-liquid lens system which makes use of an inline, transparent electroactive polymer actuator. The lens requires only a minimal number of components: a frame, a passive membrane, a dielectric elastomer actuator membrane, and a clear liquid. The focal length variation was recorded to be greater than 100% with this system, responding in less than one second. Through the analysis of membrane deformation within geometrical constraints, it is shown that by selecting appropriate lens dimensions, even larger focusing dynamic ranges can be achieved.
Proposal for Piece In Hand Matrix Ver.2: General Concept for Enhancing Security of Multivariate Public Key Cryptosystems. (2006)

We proposed the concept, piece in hand (soldiers in hand) matrix and have developed the framework based on the concept so far. The piece in hand matrix is a general concept which can be applicable to any type of multivariate public key cryptosystems to enhance their security. In this paper, we make improvements in the PH matrix method as follows. (i) In the PH matrix method, an arbitrary number of additional variables can be introduced to the random polynomial term in the public key, which is eliminated by the multiplication of the PH matrix to the public key in the decryption. Thus these additional variables enables the public key to have more than one solution, and therefore increases the difficulty to solve the public key. We show, in an experimental manner, that the PH matrix method improved in this way is secure even against the Gröbner basis attack. (ii) In the nonlinear PH matrix method proposed previously, the degree of polynomials in the public key is more than two, and this may cause an undesirable increase in the length of the public key. In this paper, we propose a nonlinear PH matrix method, where the degree of the public key is kept the same as the degree of the public key of the original cryptosystem, which is normally two.
COMPUTED TOMOGRAPHY IN CREPITANT MYONECROSIS (1993)

We report an unusual case of non-traumatic myonecrosis presenting as hip pain. Computed tomography helped to define the extent of the infection and its origin in the presacral space. The use of CT in diagnosis and management of gas-forming soft tissue infection is reviewed.
Correlation of apoptosis with change in intracellular labile Zn(II) using zinquin [(2-methyl-8-p-toluenesulphonamido-6-quinolyloxy)acetic acid], a new specific fluorescent probe for Zn(II) (1993)

Zinquin [(2-methyl-8-p-toluenesulphonamido-6-quinolyloxy)-acetic acid], a membrane-permeant fluorophore specific for Zn(II), was used with spectrofluorimetry and video image analysis to reveal and quantify labile intracellular Zn. Zinquin labelled human chronic-lymphocytic-leukaemia lymphocytes, rat splenocytes and thymocytes with a weak diffuse fluorescence that was quenched when intracellular Zn was chelated with NNN'N'-tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN) and was greatly intensified by pretreatment of cells with the Zn ionophore pyrithione and exogenous Zn. There was substantial heterogeneity of labile Zn among ionophore-treated cells, and fluorescence was largely extranuclear. The average contents of labile Zn in human leukaemic lymphocytes, rat splenocytes and rat thymocytes were approx. 20, 31 and 14 pmol/10(6) cells respectively. Morphological changes and internucleosomal DNA fragmentation indicated substantial apoptosis in these cells when the level of intracellular labile Zn was decreased by treatment with TPEN. Conversely, increasing labile Zn by pretreatment with Zn plus pyrithione suppressed both spontaneous DNA fragmentation and that induced by the potent apoptosis-induced agents colchicine and dexamethasone. These results suggest that prevention of apoptosis is a function of labile Zn, and that a reduction below a threshold concentration in this Zn pool induces apoptosis.
T3-p28 is a protein associated with the delta and epsilon chains of the T cell receptor-T3 antigen complex during biosynthesis. (1987)

The human T cell receptor-T3 antigen complex is composed of at least five polypeptide chains. In addition to the 45-kDa/50-kDa heterodimer (alpha and beta chains) of the T cell receptor, the complex includes 25-kDa (T3-gamma) and 20-kDa (T3-delta) glycoproteins and a nonglycosylated 20-kDa (T3-epsilon) protein. Here we report that in pulse-chase biosynthetic labeling experiments we detect a new polypeptide chain (T3-p28) which is associated with the T3-delta and T3-epsilon chains during biosynthesis but not on the cell surface. T3-p28, which is not recognized by anti-T3 antibodies, can be chemically distinguished from the previously described T3-gamma chain. The carboxylic ionophore monensin blocks the apparent dissociation of T3-p28 from the T3-delta and T3-epsilon chains. Peripheral blood lymphocytes as well as all T cell leukemic lines tested contain T3-p28, except one HPB-ALL subline. Since the T3-p28 protein is only observed early in biosynthesis of T3-delta and T3-epsilon, it may function in intracellular transport or assembly of the T cell receptor-T3 complex.
Pancreatic cyst ablation: why are we not doing more of these procedures? (2017)

See also: Long-term outcomes after endoscopic ultrasound-guided ablation of pancreatic cysts Endoscopy eFirstDOI: 10.1055/s-0043-110030
Design considerations for implementation of large scale automatic meter reading systems (1995)

This paper discusses the requirements imposed on the design of a power system automatic meter reading system expected to serve a large (>1 million) customer base spread over a large geographical area. Issues such as system throughput, response time, and multi-application expandability are addressed, all of which are intimately dependent on the underlying communication system infrastructure, the local geography, the customer base, and the regulatory environment. A methodology for analysis, assessment, and design of large systems is presented. For illustration, two communication systems-a low power RF/PLC system and a power frequency carrier system-are analysed and discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Flow Cytometric Characterization of Tumor-associated Macrophages in Experimental Gliomas (2000)

More abundant than macrophages and scattered throughout the central nervous system, microglia account for a significant component of the inflammatory response to experimental gliomas. A better understanding of microglial function in gliomas may be important in the development of immunotherapy strategies.
Motion and context sensing techniques for pen computing (2013)

We explore techniques for a slender and untethered stylus prototype enhanced with a full suite of inertial sensors (three-axis accelerometer, gyroscope, and magnetometer). We present a taxonomy of enhanced stylus input techniques and consider a number of novel possibilities that combine motion sensors with pen stroke and touchscreen inputs on a pen + touch slate. These inertial sensors enable motion-gesture inputs, as well sensing the context of how the user is holding or using the stylus, even when the pen is not in contact with the tablet screen. Our initial results suggest that sensor-enhanced stylus input offers a potentially rich modality to augment interaction with slate computers.