gebhart/patrepeval huggingface dataset:
Sirtuin inhibition protects from the polyalanine muscular dystrophy protein PABPN1 (2008)

Oculopharyngeal muscular dystrophy (OPMD) is caused by polyalanine expansion in nuclear protein PABPN1 [poly(A) binding protein nuclear 1] and characterized by muscle degeneration. Druggable modifiers of proteotoxicity in degenerative diseases, notably the longevity modulators sirtuins, may constitute useful therapeutic targets. However, the modifiers of mutant PABPN1 are unknown. Here, we report that longevity and cell metabolism modifiers modulate mutant PABPN1 toxicity in the muscle cell. Using PABPN1 nematodes that show muscle cell degeneration and abnormal motility, we found that increased dosage of the sirtuin and deacetylase sir-2.1/SIRT1 exacerbated muscle pathology, an effect dependent on the transcription factor daf-16/FoxO and fuel sensor aak-2/AMPK (AMP-activated protein kinase), while null mutants of sir-2.1, daf-16 and aak-2 were protective. Consistently, the Sir2 inhibitor sirtinol was protective, whereas the Sir2 and AMPK activator resveratrol was detrimental. Furthermore, rescue by sirtinol was dependent on daf-16 and not aak-2, whereas aggravation by resveratrol was dependent on aak-2 and not daf-16. Finally, the survival of mammalian cells expressing mutant PABPN1 was promoted by sirtinol and decreased by resveratrol. Altogether, our data identify Sir2 and AMPK inhibition as therapeutic strategies for muscle protection in OPMD, extending the value of druggable proteins in cell maintenance networks to polyalanine diseases.
The molecular electronic device and the biochip computer: present status. (1985)

The idea that a single molecule might function as a self-contained electronic device has been of interest for some time. However, a fully integrated version--the biochip or the biocomputer, in which both production and assembly of molecular electronic components is achieved through biotechnology-is a relatively new concept that is currently attracting attention both within the scientific community and among the general public. In the present article we draw together some of the approaches being considered for the construction of such devices and delineate the revolutionary nature of the current proposals for molecular electronic devices (MEDs) and biochip computers (BCCs). With the silicon semiconductor conductor industry already in place and in view of the continuing successes of the lithographic process it seems appropriate to ask why the highly speculative MED or BCC has engendered such interest. In some respects the answer is paradigmatic as much as it is real. It is perhaps best stated as the promise of the realm of the molecular. Thus it is envisioned that devices will be constructed by assembly of individual molecular electronic components into arrays, thereby engineering from small upward rather than large downward as do current lithographic techniques. An important corollary of the construction technique is that the functional elements of such an array would be individual molecules rather than macroscopic ensembles. These two aspects of the MED/BCC--assembly of molecular arrays and individually accessible functional molecular units--are truly revolutionary. Both require scientific breakthroughs and the necessary principles, quite apart from the technology, remain essentially unknown. It is concluded that the advent of the MED/BCC still lies well before us. The twin criteria of utilization of individual molecules as functional elements and the assembly of such elements remains as elusive as ever. Biology engineers structures on the molecular scale but biomolecules do not seem to be imbued with useful electronic properties. Molecular beam epitaxy and thin-film techniques produce electronic devices but they "engineer down" and are currently unable to generate individual molecular units. The potential of the MED/BCC field is matched only by the obstacles that must be surmounted for its realization.
Simplified scheme for routine identification of human Staphylococcus species (1975)

From a total of 40 characters that were previously used to differentiate species of staphylococci, 13 key characters were selected to make a simplified scheme that could be easily used by the routine clinical laboratory for identifying human staphylococci. These key characters included coagulase activity, hemolysis, nitrate reduction, and aerobic acid production from fructose, xylose, arabinose, ribose, maltose, lactose, sucrose, trehalose, mannitol, and xylitol. In the simplified scheme, 924 strains of staphylococci were placed into 11 positions, each of which contained the major portion (greater than or equal to 80%) of strains of one of the recognized species. Several positions contained a rare or few uncommon strains of one or more additional species and these could be resolved on the basis of other key characters.
Pathogen Recognition by the Long Pentraxin PTX3 (2011)

Innate immunity represents the first line of defence against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs) that recognise pathogen-associated molecular patterns (PAMPs) and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a nonredundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the cross-road between innate immunity, inflammation, and female fertility. Here, we review the studies on PTX3, with emphasis on pathogen recognition and cross-talk with other components of the innate immune system.
A Neural Coding Scheme Formed by the Combined Function of Gamma and Theta Oscillations (2008)

Brain oscillations are important in controlling the timing of neuronal firing. This process has been extensively analyzed in connection with gamma frequency oscillations and more recently with respect to theta frequency oscillations. Here we review evidence that theta and gamma oscillations work together to form a neural code. This coding scheme provides a way for multiple neural ensembles to represent an ordered sequence of items. In the hippocampus, this coding scheme is utilized during the phase precession, a phenomenon that can be interpreted as the recall of sequences of items (places) from long-term memory. The same coding scheme may be used in certain cortical regions to encode multi-item short-term memory. The possibility that abnormalities in theta/gamma could underlie symptoms of schizophrenia is discussed.
Glycoforms modify the dynamic stability and functional activity of an enzyme (1994)

Glycoproteins generally consist of collections of glycosylated variants (glycoforms) in which an ensemble of different oligosaccharides is associated with each glycosylation site. Bovine pancreatic ribonuclease B occurs naturally as a mixture of five glycoforms in which the same polypeptide sequence is associated with a series of oligomannose sugars attached at the single N-glycosylation site. Individual glycoforms were prepared by exoglycosidase digestions of RNase B and analyzed directly at the protein level by capillary electrophoresis. For the first time, electrophoretically pure single glycoforms have been available to explore the possibility that different sugars might specifically modify the structure, dynamics, stability, and functional properties of the protein to which they are attached. Comparisons of the amide proton exchange rates for individual glycoforms of RNase B and unglycosylated RNase A showed that while the 3D structure was unaffected, glycosylation decreased dynamic fluctuations throughout the molecule. There was individual variation in the NH-ND exchange rates of the same protons in different glycoforms, demonstrating the effects of variable glycosylation on dynamic stability. Consistent with the overall decrease in flexibility, and with the possibility that all of the sugars may afford steric protection to susceptible sites, was the finding that each of the glycoforms tested showed increased resistance to Pronase compared with the unglycosylated protein. In a novel sensitive assay using double-stranded RNA substrate, the different glycoforms showed nearly a 4-fold variation in functional activity; molecular modeling suggested that steric factors may also play a role in modulating this interaction.
Generation of continuous and pulsed diagnostic imaging x-ray radiation using a carbon-nanotube-based field-emission cathode (2002)

X-ray radiation is widely used in medical and industrial applications. The basic design of the x-ray tube has not changed significantly in the last century. In this paper, we demonstrate that medical diagnostic x-ray radiation can be generated using a carbon nanotube (CNT)-based field-emission cathode. The device can readily produce both continuous and pulsed x-rays with a programmable wave form and repetition rate. A total emission current of 28 mA was obtained from a 0.2 cm2 area CNT cathode. The x-ray intensity is sufficient to image a human extremity at 14 kVp and 180 mAs. Pulsed x-ray with a repetition rate greater than 100 kHz was readily achieved by programming the gate voltage. The CNT-based cold-cathode x-ray technology can potentially lead to portable and miniature x-ray sources for industrial and medical applications.
Binding of a Designed Anti‐Cancer Drug to the Central Cavity of an RNA Three‐Way Junction (2013)

Getting to the heart of it: Co-crystallization of an RNA three-way junction with a cylindrical di-iron(II)-based anti-cancer drug (green) results in π-stacking interactions between the cylinder and the central base pairs of the RNA structure. The shape, size, and cationic nature of the cylinder were found to be responsible for this perfect fit. Native gel electrophoresis studies confirmed stabilization of the RNA three-way junction by the iron(II) cylinder.
Maximizing tumour exposure to anti‐neuropilin‐1 antibody requires saturation of non‐tumour tissue antigenic sinks in mice (2011)

These results indicate that saturation of non-tumour tissue uptake is required in order to achieve tumour uptake and acceptable exposure to antibody. Utilization of a rodent and primate cross-binding antibody allows for translation of these results to clinical settings.
Tissue-specific codon usage and the expression of human genes (2004)

A diverse array of mechanisms regulate tissue-specific protein levels. Most research, however, has focused on the role of transcriptional regulation. Here we report systematic differences in synonymous codon usage between genes selectively expressed in six adult human tissues. Furthermore, we show that the codon usage of brain-specific genes has been selectively preserved throughout the evolution of human and mouse from their common ancestor. Our findings suggest that codon-mediated translational control may play an important role in the differentiation and regulation of tissue-specific gene products in humans.
The phase-controlled Raman effect (2013)

Unlike spontaneous Raman effect, nonlinear Raman scattering generates fields with a well-defined phase, allowing Raman signals from individual scatterers to add up into a highly directional, high-brightness coherent beam. Here, we show that the phase of coherent Raman scattering can be accurately controlled and finely tuned by using spectrally and temporally tailored optical driver fields. In our experiments, performed with spectrally optimized phase-tunable laser pulses, such a phase control is visualized through the interference of the coherent Raman signal with the field resulting from nonresonant four-wave mixing. This interference gives rise to Fano-type profiles in the overall nonlinear response measured as a function of the delay time between the laser pulses, featuring a well-resolved destructive-interference dip on the dark side of the Raman peak. This phase-control strategy is shown to radically enhance the coherent response from weak Raman modes, thus helping confront long-standing challenges in nonlinear Raman imaging and microspectroscopy.
A 64K EPROM using scaled MOS technology (1980)

This paper will report on a 64Kb static MOS EPROM which combines a two-layer poly self-aligned memory cell together with scaled NMOS periphery technology. Cell size is 0.24μm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> /b. Access time is 200ns.
6-Ethynylthieno[3,2-d]- and 6-ethynylthieno[2,3-d]pyrimidin-4-anilines as tunable covalent modifiers of ErbB kinases (2008)

Analysis of the x-ray crystal structure of mono-substituted acetylenic thienopyrimidine 6 complexed with the ErbB family enzyme ErbB-4 revealed a covalent bond between the terminal carbon of the acetylene moiety and the sulfhydryl group of Cys-803 at the solvent interface. The identification of this covalent adduct suggested that acetylenic thienopyrimidine 6 and related analogs might also be capable of forming an analogous covalent adduct with EGFR, which has a conserved cysteine (797) near the ATP binding pocket. To test this hypothesis, we treated a truncated, catalytically competent form of EGFR (678-1020) with a structurally related propargylic amine (8). An investigation of the resulting complex by mass spectrometry revealed the formation of a covalent complex of thienopyrimidine 8 with Cys-797 of EGFR. This finding enabled us to readily assess the irreversibility of various inhibitors and also facilitated a structure-activity relationship understanding of the covalent modifying potential and biological activity of a series of acetylenic thienopyrimidine compounds with potent antitumor activity. Several ErbB family enzyme and cell potent 6-ethynyl thienopyrimidine kinase inhibitors were found to form covalent adducts with EGFR.
Immunoassay of 6-Hydroxymelatonin Sulfate in Human Plasma and Urine: Abolition of the Urinary 24-Hour Rhythm with Atenolol* (1985)

An assessment of the rhythmic characteristics of melatonin secretion in man and other species requires the determination of 24-h secretion profiles. Measurement of a major excreted metabolite would allow noninvasive study of pineal function, applicable in particular to pediatric and long term circadian rhythm studies. This report describes a simple and rapid RIA for 6-hydroxymelatonin sulfate in human plasma and urine. Physiological studies revealed that both plasma and urinary levels of 6-hydroxymelatonin sulfate were closely related to plasma melatonin, and that the urinary 24-h rhythm was abolished by the beta 1-adrenergic anagonist atenolol.
Data replicas in distributed information services (1989)

In an information distribution network in which records are repeatedly read, it is cost-effective to keep read-only copies in work locations. This paper presents a method of updating replicas that need not be immediately synchronized with the source data or with each other. The method allows an arbitrary mapping from source records to replica records. It is fail-safe, maximizes workstation autonomy, and is well suited to a network with slow, unreliable, and/or expensive communications links. The algorithm is a manipulation of queries, which are represented as short encodings. When a response is generated, we record which portion of the source database was used. Later, when the source data are updated, this information is used to identify obsolete replicas. For each workstation, the identity of obsolete replicas is saved until a workstation process asks for this information. This workstation process deletes each obsolete replica, and replaces it by an up-to-date version either promptly or the next time the application asks for this particular item. Throughout, queries are grouped so that the impact of each source update transaction takes effect atomically at each workstation. Optimizations of the basic algorithm are outlined. These overlap change dissemination with user service, allow the mechanism to be hidden within the data delivery subsystem, and permit very large networks.
Dynamic leakage cut-off scheme for low-voltage SRAM's (2002)

The operation voltage of VLSIs is ever decreasing due to the strong needs for low-power consumption. In order to achieve low-voltage, high-speed operation, the CMOS process tends to be optimized for low-voltage operation using thinner gate oxide and shorter effective channel length. The low-voltage operation is also important in the future VLSIs, where scaled MOSFETs can be operated only in low V/sub DD/ environments with sufficient reliability. Low-voltage SRAM schemes have been proposed, including source voltage driving and dynamic boost of the supply voltage and word line. However, in these schemes the gate voltage of MOSFETs goes up to over 1.4 V even though the V/sub DD/ is 0.8 V, which gives rise to reliability issues in these cases. In this paper, a sub-volt SRAM circuit scheme is presented which speeds up the conventional low-voltage SRAM by more than a factor of two without applying excessive voltage to gate oxide and with maintaining the subthreshold leakage current to a tolerable level.
Parallel VLSI architectures for a class of LDPC codes (2003)

This paper presents high-performance encoder and decoder architectures for a class of low density parity check (LDPC) codes. The codes considered here are based on the parallelly concatenated parity check encoder structure. A major advantage of these codes is that the generator matrix and the parity check matrix are both sparse, which leads to efficient VLSI implementations for the encoder and the decoder. Our designs use 6-bit quantization with a code rate of 8/9 and a block size of 576 bits. An evaluation of the speed and hardware complexity is given, and simulation results for the bit error rate are obtained.
Th2-Induced Eotaxin Expression and Eosinophilia Coexist with Th1 Responses at the Effector Stage of Lung Inflammation (1998)

The T cell-mediated lung inflammation that is associated with allergic asthma is characterized mainly by massive eosinophil infiltration, which induces airway injury and the subsequent late-phase reactivity. Because Th2 cells are often isolated from asthmatic subjects, these cells are postulated to play a role in asthma pathogenesis. We report that adoptively transferred, influenza hemagglutinin-specific Th1 and Th2 cells induced different patterns of chemokines leading to different types of cellular infiltration. Th2 cells were sufficient to induce dramatic Ag-dependent lung eosinophilia and eotaxin expression; by contrast, Th1 transfer primarily induced neutrophil recruitment with little eotaxin production. To determine whether Th1 cells show inhibitory effects on Th2 cell-mediated responses, Th1 and Th2 cells were cotransferred. Hemagglutinin-specific Th1 cells did not inhibit Ag-induced lung eosinophilia, nor did they inhibit eotaxin expression. Furthermore, influenza virus infection of the lung in mice receiving hemagglutinin-specific Th2 cells also induced eotaxin expression and eosinophilia that could not be inhibited by the cotransfer of Th1 cells. Our results show that Th2-mediated allergic lung inflammation coexists with the Th1-mediated responses that are stimulated by diverse forms of Ags.
A functionally distributed responsive micro controller for distributed real-time processing (2002)

We propose a functionally distributed responsive (reactive in real-time) microcontroller for distributed real-time processing, which can control personal robots, home automation, office automation, etc. A responsive controller is composed of a mother module and an I/O card customizable for its specific application. A common mother module is composed of a processor, a memory system, an I/O card bus interface for its daughter card, and high-speed real-time links called responsive links. In order to realize hard real-time communication needed for robot control, sensing, etc., a responsive link consists of a pair of full-duplex data lines and two-way event lines. Many kinds of systems can be flexibly composed by connecting any number of the responsive controllers using the responsive links.
Popliteal Artery Trauma (1980)

Injury to the popliteal artery is the most common cause of amputation in injured extremities. A six-year experience (1974-1979) at Cook County Hospital, Chicago, involved 31 popliteal artery injuries without amputation. Penetrating trauma was the most frequent cause of injury; however, a considerable number of blunt trauma injuries with fractures and dislocations were also present. Prolonged ischemic time was not a deterrent to successful vascular reconstruction. The recognition of compartmental hypertension and performance of fasciotomy before vascular repair were credited as major factors in our success. The use of interposition saphenous vein graft in the arterial reconstruction, repair of concomitant popliteal vein injuries, initial bone fixation of fractures with external fixators, and the performance of intraoperative arteriography were all important steps taken to ensure a 100% limb salvage.
Camera identification from cropped and scaled images (2008)

In this paper, we extend our camera identification technology based on sensor noise to a more general setting when the image under investigation has been simultaneously cropped and scaled. The sensor fingerprint detection is formulated using hypothesis testing as a two-channel problem and a detector is derived using the generalized likelihood ratio test. A brute force search is proposed to find the scaling factor which is then refined in a detailed search. The cropping parameters are determined from the maximum of the normalized cross-correlation between two signals. The accuracy and limitations of the proposed technique are tested on images that underwent a wide range of cropping and scaling, including images that were acquired by digital zoom. Additionally, we demonstrate that sensor noise can be used as a template to reverse-engineer in-camera geometrical processing as well as recover from later geometrical transformations, thus offering a possible application for re-synchronizing in digital watermark detection.
Tree-Structured Semantic Encoder with Knowledge Sharing for Domain Adaptation in Natural Language Generation (2019)

Domain adaptation in natural language generation (NLG) remains challenging because of the high complexity of input semantics across domains and limited data of a target domain. This is particularly the case for dialogue systems, where we want to be able to seamlessly include new domains into the conversation. Therefore, it is crucial for generation models to share knowledge across domains for the effective adaptation from one domain to another. In this study, we exploit a tree-structured semantic encoder to capture the internal structure of complex semantic representations required for multi-domain dialogues in order to facilitate knowledge sharing across domains. In addition, a layer-wise attention mechanism between the tree encoder and the decoder is adopted to further improve the model's capability. The automatic evaluation results show that our model outperforms previous methods in terms of the BLEU score and the slot error rate, in particular when the adaptation data is limited. In subjective evaluation, human judges tend to prefer the sentences generated by our model, rating them more highly on informativeness and naturalness than other systems.