gebhart/patrepeval huggingface dataset:
3D modeling of chromosomes territories in normal and aneuploid nuclei (2018)

DNA is packaged into chromosomes, which occupy a specific region in the three-dimensional (3D) nuclear space known as the chromosome territories (CTs). The spatial organization (SO) of CTs within the nucleus is non-random and any disruption of this organization leads to undesired changes, such as disease states. Determining how CTs organize in the nucleus can allow us to unravel any changes occurring during aneuploidy (loss or gain of chromosomes), a hallmark of cancer. Here, we describe a 3D modeling approach to allow precise shape estimation and localization of CTs in the nucleus of human embryonic stem cells (hES) undergoing progressive but defined aneuploidy. The hES cell line WA09 acquires an extra copy of chromosome 12 in culture with increasing passages. Both diploid and aneuploid nuclei were analyzed to quantitate the differences in the localization of CTs for chromosome 12 as it transitions from euploidy to aneuploidy. The CTs were detected with chromosome specific DNA probes via multi-color fluorescence in situ hybridization (FISH) in conjunction with confocal microscopy. We then employed spherical harmonic (SPHARM) surface modeling to generate a well-defined 3D surface for both the nuclei and enclosed CTs, thereby allowing precise quantification of their size and shape. The estimated models were compared across multiple cells by aligning the nuclei to a well-defined template followed by determining CT position with respect to a local landmark. Our results present evidence of statistically significant changes in the relative positioning of CTs in trisomy-12 cells when compared to diploid cells from the same population.
Increased urinary nitrite excretion in primary enuresis: effects of indomethacin treatment on urinary and serum osmolality and electrolytes, urinary volumes and nitrite excretion (2002)

Urinary nitrite excretion increased significantly in patients with primary nocturnal enuresis; indomethacin markedly reduced bed-wetting episodes and decreased the frequency of voiding in enuretics with small or normal functional bladder capacity, which was associated with a significant decrease in urinary nitrite excretion. Indomethacin reduced bed-wetting by decreasing the urine volume, clearance of free water and urinary electrolytes, and through possible effects on bladder and urethral contraction, by inhibiting NO and prostaglandin synthesis. NO and prostaglandins might be important in the pathogenesis of primary enuresis.
Complexity measures to track the evolution of a SNOMED hierarchy. (2008)

SNOMED CT is an extensive terminology with an attendant amount of complexity. Two measures are proposed for quantifying that complexity. Both are based on abstraction networks, called the area taxonomy and the partial-area taxonomy, that provide, for example, distributions of the relationships within a SNOMED hierarchy. The complexity measures are employed specifically to track the complexity of versions of the Specimen hierarchy of SNOMED before and after it is put through an auditing process. The pre-audit and post-audit versions are compared. The results show that the auditing process indeed leads to a simplification of the terminology's structure.
In vitro–transcribed guide RNAs trigger an innate immune response via the RIG-I pathway (2018)

Clustered, regularly interspaced, short palindromic repeat (CRISPR)-CRISPR-associated 9 (Cas9) genome editing is revolutionizing fundamental research and has great potential for the treatment of many diseases. While editing of immortalized cell lines has become relatively easy, editing of therapeutically relevant primary cells and tissues can remain challenging. One recent advancement is the delivery of a Cas9 protein and an in vitro-transcribed (IVT) guide RNA (gRNA) as a precomplexed ribonucleoprotein (RNP). This approach allows editing of primary cells such as T cells and hematopoietic stem cells, but the consequences beyond genome editing of introducing foreign Cas9 RNPs into mammalian cells are not fully understood. Here, we show that the IVT gRNAs commonly used by many laboratories for RNP editing trigger a potent innate immune response that is similar to canonical immune-stimulating ligands. IVT gRNAs are recognized in the cytosol through the retinoic acid-inducible gene I (RIG-I) pathway but not the melanoma differentiation-associated gene 5 (MDA5) pathway, thereby triggering a type I interferon response. Removal of the 5'-triphosphate from gRNAs ameliorates inflammatory signaling and prevents the loss of viability associated with genome editing in hematopoietic stem cells. The potential for Cas9 RNP editing to induce a potent antiviral response indicates that care must be taken when designing therapeutic strategies to edit primary cells.
A FORMAÇÃO DO PROFESSOR DE GEOGRAFIA (2011)

Discute-se a formacao do professor de Geografia no contexto do papel exercido pela Educacao como um processo global.
Microstructures Related to Ferroelectric Properties in (Bi<sub>0.5</sub>K<sub>0.5</sub>)TiO<sub>3</sub>–BiFeO<sub>3</sub> (2010)

Crystal structures and microstructures associated with ferroelectric properties in a lead-free piezoelectric compound, x (Bi 0.5 K 0.5 )TiO 3 –(1- x )BiFeO 3 , have been investigated mainly by transmission electron microscopy (TEM). Complicated ferroelectric domain structures with a width of approximately ∼200 nm were found in the polar rhombohedral structure of the x = 0.30 compound. On the other hand, a tweed-like contrast, which stems from local lattice distortion, was observed in the pseudocubic structure of the x = 0.40, 0.46, and 0.50 compounds. The present results suggest that the pseudocubic phase is characterized by nanodomain structures consisting of non-polar cubic and polar rhombohedral structures.
Analog Design (2003)

Abstract The chapter addresses the design of nonprotein, nonpeptide drug analogs. Strategies and applications of classical and nonclassical bioisosteres, rigid and semirigid analogs; homologation of alkyl chains; changes in ring size and ring‐position isomers; substitution of aromatic for aliphatic rings; alteration of stereochemistry; design of fragments of lead molecules; and variation of interatomic distances are discussed. Numerous examples from the literature of each type of molecular modification are presented, together with summaries of pharmacological consequences of the modifications. Advantages and disadvantages of each category are cited.
Electro-optical circuits based on light-sensing ambipolar organic field-effect transistors (2007)

The author reports on light-sensing ambipolar organic field-effect transistors (LS-OFETs) based on blends of[6,6]-phenyl-C61-butyric acid methyl ester and poly [2-methoxy-5-(3′,7′-dimethyloctyloxy)]-p-phenylene vinylene. By carefully tuning the ambipolar transport character of the LS-OFETs, their photoresponsivity can be controlled and optimized. By combining LS-OFETs with ordinary unipolar organic transistors, fabrication of electro-optical switches and logic circuits, such as NOT and OR gates, is demonstrated. This is the only report of organic electro-optical circuits in which signal processing involves the use of both optical and electrical input signals. Such circuits could one day be explored in optical sensor array applications.
The 2.5 Å Crystal Structure of the SIRT1 Catalytic Domain Bound to Nicotinamide Adenine Dinucleotide (NAD<sup>+</sup>) and an Indole (EX527 Analogue) Reveals a Novel Mechanism of Histone Deacetylase Inhibition (2013)

The sirtuin SIRT1 is a NAD(+)-dependent histone deacetylase, a Sir2 family member, and one of seven human sirtuins. Sirtuins are conserved from archaea to mammals and regulate transcription, genome stability, longevity, and metabolism. SIRT1 regulates transcription via deacetylation of transcription factors such as PPARγ, NFκB, and the tumor suppressor protein p53. EX527 (27) is a nanomolar SIRT1 inhibitor and a micromolar SIRT2 inhibitor. To elucidate the mechanism of SIRT inhibition by 27, we determined the 2.5 Å crystal structure of the SIRT1 catalytic domain (residues 241-516) bound to NAD(+) and the 27 analogue compound 35. 35 binds deep in the catalytic cleft, displacing the NAD(+) nicotinamide and forcing the cofactor into an extended conformation. The extended NAD(+) conformation sterically prevents substrate binding. The SIRT1/NAD(+)/35 crystal structure defines a novel mechanism of histone deacetylase inhibition and provides a basis for understanding, and rationally improving, inhibition of this therapeutically important target by drug-like molecules.
CaN19 expression in benign and malignant hyperplasias of the skin and oral mucosa: evidence for a role in regenerative differentiation. (1997)

CaN19, a member of the S100 family of calcium-binding proteins, is known to be "underexpressed" in cultured breast carcinoma-derived cell lines relative to their normal counterparts. By Northern blotting, we confirm these results and find that CaN19 is also markedly "underexpressed" in several carcinoma-derived cell lines of the skin, oral mucosa, and urogenital tract. However, exceptions to the inverse correlation between CaN19 expression and malignancy have been identified, bringing into question the hypothesis that CaN19 functions as a tumor suppressor gene. Unexpectedly, CaN19 mRNA was strongly expressed in bulk specimens of basal and squamous cell carcinomas of the skin and oral cavity. However, in situ hybridization revealed only limited CaN19 expression in tumor cells themselves; the bulk of expression is localized to hyperplastic perilesional epidermis. Tumor cell expression of CaN19 was similar in primary and locally metastatic tumors, indicating that this gene is not necessarily down-regulated during tumor progression. Coordinate overexpression of CaN19 and the "hyperproliferalive" keratin K6a was observed only in tissues undergoing squamous differentiation. Taken together with other recent results from our laboratory, these findings suggest the hypothesis that CaN19 participates in an epidermal growth factor receptor-dependent pathway of regenerative squamous differentiation.
Designing Transparent Flexible-Grid Optical Networks for Maximum Spectral Efficiency [Invited] (2017)

Higher-order modulation formats and spectral super-channels are key to maximizing spectral efficiency (SE) in next-generation optical transport networks, thereby postponing/minimizing expensive additional fiber rollouts and reconfigurable optical add/drop multiplexer node upgrades. A flexible dense wavelength division multiplexed (DWDM) grid is key to efficiently accommodating media channels requiring more (or less) than 50 GHz of contiguous spectrum. In particular, routing media channels consisting of multiple adjacent carriers enables packing them closer together and sharing a single pair of guard bands of adaptive width to cope with optical filtering. This effect is maximized by giving preference to deploying media channels with more carriers. However, designing the DWDM network in such a way can translate into resource overprovisioning whenever the traffic requirements between two nodes are below the (large) capacity of the most spectrally efficient media channel format that can be deployed between those nodes. This paper provides insight on how the set of media channels and the network design framework used impact the trade-off between maximizing SE and minimizing resource overprovisioning in transparent flexible-grid optical networks. Furthermore, it discusses enabling strategies to mitigate the risk of resource overprovisioning when maximizing network SE is the key design objective.
Treatment of overdose in the synthetic opioid era (2021)

Overdose deaths are often viewed as the leading edge of the opioid epidemic which has gripped the United States over the past two decades (Skolnick, 2018a). This emphasis is perhaps unsurprising because opioid overdose is both the number-one cause of death for individuals between 25 and 64 years old (Dezfulian et al., 2021) and a significant contributor to the decline in average lifespan (Dowell et al., 2017). Exacerbated by the COVID 19 pandemic, it was estimated there were 93,400 drug overdose deaths in the United States during the 12 months ending December 2020, with more than 69,000 (that is, >74%) of these fatalities attributed to opioid overdose (Ahmad et al., 2021). However, the focus on mortality statistics (Ahmad et al., 2021; Shover et al., 2020) tends to obscure the broader medical impact of nonfatal opioid overdose. Analyses of multiple databases indicate that for each opioid-induced fatality, there are between 6.4 and 8.4 non-fatal overdoses, exacting a significant burden on both the individual and society. Over the past 7-8 years, there has been an alarming increase in the misuse of synthetic opioids ("synthetics"), primarily fentanyl and related piperidine-based analogs. Within the past 2-3 years, a structurally unrelated class of high potency synthetics, benzimidazoles exemplified by etonitazene and isotonitazene ("iso"), have also appeared in illicit drug markets (Thompson, 2020; Ujvary et al. 2021). In 2020, it was estimated that over 80% of fatal opioid overdoses in the United States now involve synthetics (Ahmad et al., 2021). The unique physicochemical and pharmacological properties of synthetics described in this review are responsible for both the morbidity and mortality associated with their misuse as well as their widespread availability. This dramatic increase in the misuse of synthetics is often referred to as the "3rd wave" (Pardo et al., 2019; Volkow and Blanco, 2020) of the opioid epidemic. Among the consequences resulting from misuse of these potent opioids is the need for higher doses of the competitive antagonist, naloxone, to reverse an overdose. The development of more effective reversal agents such as those described in this review is an essential component of a tripartite strategy (Volkow and Collins, 2017) to reduce the biopsychosocial impact of opioid misuse in the "synthetic era".
Self-Heating Synthesis Of Materials (1991)

Gallium is a metal that literally melts in your hand. It has low toxicity, near-zero vapor pressure, and a viscosity similar to water. Despite possessing a surface tension larger than any other liquid (near room temperature), gallium can form nonspherical ...Read More
Regulation of bovine brain microvascular endothelial tight junction assembly and barrier function by laminar shear stress (2007)

Blood-brain barrier (BBB) controls paracellular solute diffusion into the brain microenvironment and is maintained primarily by tight junctions between adjacent microvascular endothelial cells. Studies implicate blood flow-associated shear stress as a pathophysiological mediator of BBB function, although detailed biochemical data are scarce. We hypothesize that shear stress upregulates BBB function via direct modulation of expression and properties of pivotal tight-junction proteins occludin and zonula occludens-1 (ZO-1). Bovine brain microvascular endothelial cells (BBMvECs) were exposed to either steady or pulsatile shear stress (10 and 14 dyn/cm(2), respectively) for 24 h. Sheared BBMvECs were monitored for occludin-ZO-1 expression, association, and subcellular localization, and transendothelial permeability of BBMvECs to FITC-dextran and (14)[C]sucrose was assessed. Actin reorganization and BBMvEC realignment were observed following steady shear stress for 24 h. Substantial increases in occludin mRNA and protein expression (2.73 +/- 0.26- and 1.83 +/- 0.03-fold) and in occludin-ZO-1 association (2.12 +/- 0.15-fold) were also observed. Steady shear stress also induced clear relocalization of both proteins to the cell-cell border in parallel with reduced transendothelial permeability to FITC-dextran (but not sucrose). Following pulsatile shear stress, increased protein levels for both occludin and ZO-1 (2.15 +/- 0.02- and 1.67 +/- 0.21-fold) and increased occludin-ZO-1 association (2.91 +/- 0.14-fold) were observed in parallel with a reduction in transendothelial permeability to (14)[C]sucrose. Shear stress upregulates BBMvEC barrier function at the molecular level via modulation of expression, association, and localization of occludin and ZO-1. The pulsatile shear model appeared to give the most profound biochemical responses.
3 Gbps, 5000 ppm spread spectrum SerDes PHY with frequency tracking phase interpolator for serial ATA (2004)

We have developed a 5000 ppm spread spectrum Serializer/Deserializer (SerDes) physical layer (PHY) chip compliant with Serial AT Attachment (ATA). The chip was fabricated with a 0.15 /spl mu/m 1.5 V CMOS process and includes a self-running spread spectrum carrier generator to provide both transmit and receive block, a self-running phase interpolator to recover the +/-5000 ppm spread spectrum receive (RX) clock and data.
Synergistic effect of antithrombin III, activated protein C and heparin on the inhibition of the tissue thromboplastin-mediated coagulation. (1989)

The synergistic effect of antithrombin III (ATIII), activated protein C (APC) and heparin on the tissue thromboplastin (TP)-mediated coagulation cascade was studied. APC prolonged the activated partial thromboplastin time of human plasma with increasing APC concentration but affected the prothrombin time only slightly. Neither ATIII nor heparin prolonged the prothrombin time by itself, while a mixture of APC and heparin strongly inhibited the coagulation. When the effects of APC, heparin and ATIII on the TP-mediated coagulation were examined with a solution consisting of prothrombin, factor V, factor VII, factor X and fibrinogen at physiological concentrations, the coagulation time was prolonged only slightly by the APC-heparin or ATIII-heparin mixture. However, the coagulation time was prolonged markedly by simultaneous addition of APC, ATIII and heparin to the solution. Inhibition of thrombin activity by the ATIII-APC-heparin mixture was weak as compared with that by the ATIII-heparin mixture after a 1-min incubation, but after a 2-min incubation the inhibitory activities were equal. Suppression of thrombin activity by the ATIII-APC-heparin mixture was supposed to be due to the inhibition of the interaction between ATIII and heparin on thrombin by APC because the APC-ATIII-heparin complex was detected by crossed immuno-electrophoresis but not by sodium dodecyl sulfate (SDS)-polyacrylamide electrophoresis. When the inhibitory effect of APC alone or the APC-heparin mixture on the platelet prothrombin converting activity (PPCA) was examined, heparin accelerated the PPCA inhibition by APC.(ABSTRACT TRUNCATED AT 250 WORDS)
GENE EXPRESSION PROFILE OF INFLAMMATORY NEUTROPHILS: ALTERATIONS IN THE INHIBITORS OF APOPTOSIS PROTEINS DURING SPONTANEOUS AND DELAYED APOPTOSIS (2004)

Inflammatory mediators delay neutrophil apoptosis, which contributes to the persistence of inflammation. The mechanisms responsible for this delay and resistance to Fas antibody-induced apoptosis are unknown but are dependent on protein synthesis. These proteins have been shown to inhibit caspase activity central to the induction of apoptosis. The inhibitors of apoptosis proteins have been shown to inhibit caspase activity and prevent apoptosis in a number of cellular systems. We hypothesize that the regulation of neutrophil apoptosis is dependent on the expression of the IAPs. c-IAP-1, c-IAP-2, and XIAP are expressed in the neutrophil at both the mRNA and protein level, but their relative protein expression is low compared with other cell types. The in vitro aging of human neutrophils results in their induction of apoptosis, which is associated with the loss of c-IAP-1 expression. The pancaspase inhibitor (zVAD-FMK) and LPS, which delay spontaneous apoptosis, also prevented this loss of c-IAP-1. Gene chip microarrays have shown that LPS increases c-IAP-1 and c-IAP-2 mRNA expression in neutrophils. However, this does not correspond to an increase in protein. Neutrophils from septic patients with delayed apoptosis show an increase in XIAP, with no change in cIAP-1 or cIAP-2 mRNA, demonstrating that different mechanisms contribute to the delay in neutrophil apoptosis. This study demonstrates that the loss of IAP expression may facilitate the induction of neutrophil apoptosis, and preventing this loss of IAP expression may represent a more significant contribution to delayed apoptosis rather than an increase in their expression.
New methods and reagents in organic synthesis. 31. Lithium trimethylsilyldiazomethane: A new synthon for the preparation of tetrazoles. (1982)

Lithium trimethylsilyldiazomethane, prepared from trimethylsilyldiazomethane and lithium diisopropylamide, reacts smoothly with methyl esters of carboxylic acids to give 2-substituted 5-trimethylsilyltetrazoles in good yields.
Rate Balancing in Multiuser MIMO OFDM Systems (2009)

Recently, the capacity region of the Gaussian broadcast channel has been characterized. For a given transmit power constraint, those points on the boundary of the capacity region can be regarded as the set of optimal operational points. The present work addresses the problem of selecting the point within this set that satisfies given constraints on the ratios between rates achieved by the different users in the network. This problem is usually known as rate balancing. To this end, the optimum iterative approach for general MIMO channels is revisited and adapted to an OFDM transmission scheme. Specifically, an algorithm is proposed that exploits the structure of the OFDM channel and whose convergence speed is essentially insensitive to the number of subcarriers. This is in contrast to a straightforward extension of the general MIMO algorithm to an OFDM scheme. Still, relatively high complexity and the need of a time-sharing policy to reach certain rates are at least two obstacles for a practical implementation of the optimum solution. Based on a novel decomposition technique for broadcast channels a suboptimum non-iterative algorithm is introduced that does not require time-sharing and very closely approaches the optimum solution.
Manifestations and mechanisms of radiation-induced genomic instability in V-79 Chinese hamster cells (1998)

The results indicate that non-lethal radiation damage to an extranuclear target leads to a persistent increase in clastogenic activity in the surviving irradiated cells.
Memory-Aware Embedded Control Systems Design (2016)

Control applications are often implemented on highly cost-sensitive and resource-constrained embedded platforms, such as microcontrollers with a small on-chip memory. Typically, control algorithms are designed using model-based approaches, where the details of the implementation platform are completely ignored. As a result, optimizations that integrate platform-level characteristics into the control algorithms design are largely missing. With the emergence of cyber-physical systems (CPS)-oriented thinking, there has lately been a strong interest in co-design of control algorithms and their implementation platforms, leading to work on networked control systems and computation-aware control algorithms design. However, there has so far been no work on integrating the characteristics of a memory architecture into the design of control algorithms. In this paper we, for the first time, show that accounting for the impact of on-chip memory (or cache) reuse on the performance of control applications motivates new techniques for control algorithms design. This leads to significant improvement in quality of control for given resource availability, or more efficient implementations of embedded control applications. We believe that this paper opens up a variety of possibilities for memory-related optimizations of embedded control systems, that will be pursued by researchers working on computer-aided design for CPS.
Broadband discrete fiber Raman amplifier with high differential gain operating over 1.65 μm-band (2002)

A high differential-gain (0.08 dB/mW), low-noise ( < 5.0 dB), broadband (30 nm) and flat-gain ( < ±1 dB) fiber Raman amplifier operating over the 1.65 μm-band has been demonstrated employing a low-loss highly nonlinear fiber and a broadened pump light source.