gebhart/patrepeval huggingface dataset:
Advances in Polymer Design for Enhancing Oral Drug Solubility and Delivery (2018)

Synthetic polymers have enabled amorphous solid dispersions (ASDs) to emerge as an oral delivery strategy for overcoming poor drug solubility in aqueous environments. Modern ASD products noninvasively treat a range of chronic diseases (for example, hepatitis C, cystic fibrosis, and HIV). In such formulations, polymeric carriers generate and maintain drug supersaturation upon dissolution, increasing the apparent drug solubility to enhance gastrointestinal barrier absorption and oral bioavailability. In this Review, we outline several approaches in designing polymeric excipients to drive interactions with active pharmaceutical ingredients (APIs) in spray-dried ASDs, highlighting polymer-drug formulation guidelines from industrial and academic perspectives. Special attention is given to new commercial and specialized polymer design strategies that can solubilize highly hydrophobic APIs and suppress the propensity for rapid drug recrystallization. These molecularly customized excipients and hierarchical excipient assemblies are promising toward informing early-stage drug-discovery development and reformulating existing API candidates into potentially lifesaving oral medicines for our growing global population.
Advanced Molecular Design of Functional Soft Materials (2014)

Owing to a tremendous progress in supramolecular chemistry, one can now construct and tailor a variety of desired nanostructures, where assembling events involved mostly operate thermodynamically. On the other hand, if one may consider developing materials for practical applications, we certainly need to design kinetically preferred hierarchical structures. However, there is no rational molecular design strategy for this issue. Here we report some of our recent achievements related to this issue. The first topic focuses on how one can translate a tiny molecular motion into a macroscopic motion. [1] We found that, by hot pressing using unidirectionally drawn Teflon sheets, a polymer brush containing triply connected azobenzene units in its side chains form a hierarchically ordered bimorph film, where all the cylindrical brush objects align homeotropically with respect to the film plane, and the film shows a macroscopic photomechanical motion. The second topic features the development of &amp;apos;aqua material&amp;apos;, characterized by an ultralow content of organic components and an ultrahigh content of water. [2] This
Rate Analysis of Two-Receiver MISO Broadcast Channel with Finite Rate Feedback: A Rate-Splitting Approach (2015)

To enhance the multiplexing gain of two-receiver Multiple-Input-Single-Output Broadcast Channel with imperfect channel state information at the transmitter (CSIT), a class of Rate-Splitting (RS) approaches has been proposed recently, which divides one receiver's message into a common and a private part, and superposes the common message on top of Zero-Forcing precoded private messages. In this paper, with quantized CSIT, we study the ergodic sum rate of two schemes, namely RS-S and RS-ST, where the common message(s) are transmitted via a space and space-time design, respectively. Firstly, we upper-bound the sum rate loss incurred by each scheme relative to Zero-Forcing Beamforming (ZFBF) with perfect CSIT. Secondly, we show that, to maintain a constant sum rate loss, RS-S scheme enables a feedback overhead reduction over ZFBF with quantized CSIT. Such reduction scales logarithmically with the constant rate loss at high Signal-to-Noise-Ratio (SNR). We also find that, compared to RS-S scheme, RS-ST scheme offers a further feedback overhead reduction that scales with the discrepancy between the feedback overhead employed by the two receivers when there are alternating receiver-specific feedback qualities. Finally, simulation results show that both schemes offer a significant SNR gain over conventional single-user/multiuser mode switching when the feedback overhead is fixed.
<title>Rewritable optical disk system with over 10 GB of capacity</title> (1998)

Using a two-element objective lens, over 0.9 NA lens and long WD lens are demonstrated. Using a thin cover layer, problems for skew margin and thickness tolerance are solved. Using a red LD, a 0.85 NA lens and a 0.1 mm cover PC disk, 8 GB rewritable disk system has been developed. Using a blue-green LD and an SHG blue laser, promising results are demonstrated for 12 GB and 17 GB of capacity.
High voltage machine mainwall insulation material behavior when exposed to raw natural gas (2010)

Natural gas recovery from subsea fields is increased by use of artificial lift, utilizing subsea compression technology to boost the gas flow. Such machines consist of a high-speed, high voltage electrical motor integrated into the same casing as the compressor and where the motor is cooled by the process gas injected from the compressor itself. Since the insulation system is in direct contact with the process gas it has to possess excellent chemical resistance and mechanical strength to withstand rapid decompression. Various types of mica-based mainwall insulations were exposed to an environment consisting of hydrocarbon gas, condensate and a mixture of water and monoethylene glycol (MEG) at 150 bar and 130°C. Physical and mechanical parameters of the samples were evaluated. The process gas ageing tests revealed that the mechanical strength of the mainwall insulation is mainly dependent on the selected resin and the degree of resin saturation inside the insulation.
Non-traditional risk factors for atherosclerosis in high risk children. (1996)

Non-traditional risk factors for atherosclerosis were examined in children whose fathers suffered from myocardial infarction up to age 48. Factors examined were hyperinsulinemia, insulin resistance, lipoprotein(a) [Lp(a)], fibrinogen, cardiovascular hyperreactivity, and autonomic nervous system dysfunction. Hyperinsulinemia was present in five cases (9%) and hypoinsulinemia in two. Insulin output following glucose load was significantly higher in obese children compared with controls. There was an increase in Lp(a) alone in 14 cases (24%) and with low density lipoprotein in 6 cases. Increased fibrinogen and positive correlation with insulin abnormality was present in 29% (76% females) (P >0.02). Cardiac hyperreactivity (increased systolic blood pressure) was present in 9% and increased blood pressure and pulse rate in 17%. Holter monitoring pattern was sympathetic in 39% and parasympathetic in 47% of cases. Thus a number of non-traditional risk factors were found to be higher than normal in a relatively large number of children at high risk for atherosclerosis, with 25 children having more than three risk factors.
Genotype–phenotype correlations in WHIM syndrome: a systematic characterization of CXCR4WHIM variants (2022)

Warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome is a rare primary immunodeficiency predominantly caused by heterozygous gain-of-function mutations in CXCR4 C-terminus. We assessed genotype-phenotype correlations for known pathogenic CXCR4 variants and in vitro response of each variant to mavorixafor, an investigational CXCR4 antagonist. We used cell-based assays to analyze CXCL12-induced receptor trafficking and downstream signaling of 14 pathogenic CXCR4 variants previously identified in patients with WHIM syndrome. All CXCR4 variants displayed impaired receptor trafficking, hyperactive downstream signaling, and enhanced chemotaxis in response to CXCL12. Mavorixafor inhibited CXCL12-dependent signaling and hyperactivation in cells harboring CXCR4<sup>WHIM</sup> mutations. A strong correlation was found between CXCR4 internalization defect and severity of blood leukocytopenias and infection susceptibility, and between AKT activation and immunoglobulin A level and CD4<sup>+</sup> T-cell counts. This study is the first to show WHIM syndrome clinical phenotype variability as a function of both CXCR4<sup>WHIM</sup> genotype diversity and associated functional dysregulation. Our findings suggest that CXCR4 internalization may be used to assess the pathogenicity of CXCR4 variants in vitro and also as a potential WHIM-related disease biomarker. The investigational CXCR4 antagonist mavorixafor inhibited CXCL12-dependent signaling in all tested CXCR4-variant cell lines at clinically relevant concentrations.
Human VKORC1 2255T>C polymorphism: distribution analysis in a Romanian population (2012)

1 Endocrinology Chair, VIth Medical Sciences Department, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania, 2 Discipline of Ecology and Environmental Protection, University of Agricultural Sciences and Veterinary Medicine, Faculty of Animal Science and Biotechnologies, Cluj-Napoca, Romania, 3 Endocrinology Clinic, County Emergency Clinical Hospital Cluj, Cluj-Napoca, Romania.
Abstract 4499: HM5016699, a novel and selective PI3K/mTOR dual inhibitor (2011)

Abstract PI3KCA gene amplification and mutations have been identified in many types of tumors, suggesting the dysregulation of PI3K/AKT/mTOR axis plays pivotal roles in tumorigenesis and development. Reported here is the discovery of HM5016699 as a potent, reversible ATP-competitive PI3K/mTOR dual inhibitor for treatment of cancer. HM5016699 showed potent kinase inhibition with IC50 of 0.01, 0.206, 0.052, 0.051 and 0.059 µM on PI3Kα, β, γ, Δ and mTOR, respectively. It demonstrated high selectivity on PI3K family and mTOR over a panel of 274 kinases. Of the 67 tumor cell lines screened from lung, colon, breast, ovarian, and other tumor types, we found that the tumor cells with HER2 gene amplification or PTEN loss tended to be sensitive to HM5016699, while the tumor cells harboring PI3KCA mutations and wild type Ras/Raf were mostly sensitive to the compound. HM5016699 could also show p-Erk inhibition and apoptotic induction at higher concentrations in the tumor cells harboring Ras/Raf mutations, suggesting it might bring benefits to patients carrying Ras/Raf mutations in the clinic. Consistent with in vitro studies, HM5016699 exhibited dose dependent tumor growth inhibition on multiple human xenografts models. It was found that the tumors with PIK3CA mutation or PTEN deletion were highly sensitive to HM5016699 with ED50s ranging from 0.6 to 1.8 mg/kg in U87MG (pTEN null), SKOV3 (H1047) and H1975 (G118D), whereas in tumors with Ras/Raf mutations, such as DLD-1(G13D), A549 (G12S) and HT-29(V600E), its ED50s were from 3.0 to 15.0 mg/kg. The decreased phosphorylation of AKT and S6 was observed in the tumor xenograft tissues treated with HM5016699, which was well-correlated with compound exposure. Therefore, we concluded that HM5016699 demonstrated both in vitro and in vivo activity through acting on PI3K/mTOR pathway. HM5016699 exhibited a favorable pharmacokinetic profile and acceptable safety window in rats. The pre-clinical study results suggest that HM5016699 could be a promising anti-cancer agent. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4499. doi:10.1158/1538-7445.AM2011-4499
Whole miRNome-Wide Differential Co-Expression of MicroRNAs (2012)

Co-regulation of genes has been extensively analyzed, however, rather limited knowledge is available on co-regulations within the miRNome. We investigated differential co-expression of microRNAs (miRNAs) based on miRNome profiles of whole blood from 540 individuals. These include patients suffering from different cancer and non-cancer diseases, and unaffected controls. Using hierarchical clustering, we found 9 significant clusters of co-expressed miRNAs containing 2-36 individual miRNAs. Through analyzing multiple sequencing alignments in the clusters, we found that co-expression of miRNAs is associated with both sequence similarity and genomic co-localization. We calculated correlations for all 371,953 pairs of miRNAs for all 540 individuals and identified 184 pairs of miRNAs with high correlation values. Out of these 184 pairs of miRNAs, 16 pairs (8.7%) were differentially co-expressed in unaffected controls, cancer patients and patients with non-cancer diseases. By computing correlated and anti-correlated miRNA pairs, we constructed a network with 184 putative co-regulations as edges and 100 miRNAs as nodes. Thereby, we detected specific clusters of miRNAs with high and low correlation values. Our approach represents the most comprehensive co-regulation analysis based on whole miRNome-wide expression profiling. Our findings further decrypt the interactions of miRNAs in normal and human pathological processes.
Microwave Sintering and Melting of Titanium Powder for Low-Cost Processing (2010)

The emerging reduction technologies for titanium from ore produce powder instead of sponge. Conventional methods for sintering and melting of titanium powder are costly, as they are energy intensive and require high vacuum, 10-6 Torr or better, since titanium acts as a getter for oxygen at high temperature, adversely affecting mechanical properties. Other melting processes such as plasma arcs have the additional problem of electrode consumption, and direct induction heating of the titanium powder is problematic. Microwave sintering or melting in an atmospheric pressure argon gas environment is potentially cost effective and energy efficient due to the possibility of direct microwave heating of the titanium powder augmented by hybrid heating in a ceramic casket. We are investigating this approach at the Naval Research Laboratory using an S–Band microwave system. The experimental setup and the results of melting and sintering experiments will be described including a rough estimate of energy usage.
Analysis of CFTR transcripts in nasal epithelial cells and lymphoblasts of a cystic fibrosis patient with 621 +1G→T and 711 +1G→T mutations (1993)

We have analyzed the CFTR mRNA populations in a cystic fibrosis patient heterozygous for the 621 + 1G-->T and 711 + 1G-->T mutations. Total RNA isolated from the nasal epithelial cells and Epstein-Barr virus-transformed lymphoblasts derived from this patient was reversely transcribed and a region extending from exon 3 to exon 7 of the gene was amplified by the polymerase chain reaction and analyzed. Three abnormal products were identified, suggesting the presence of three aberrant transcripts, and their profiles were identical in both cell types. Two of the products were found to be missing either exon 4 or exon 5 as anticipated from the transcripts from the 621 + 1G-->T or 711 + 1G-->T alleles, respectively. The third product was apparently derived from an alternatively spliced mRNA species in the absence of the nominal splice site (in 621 + 1G-->T) through the use of a cryptic splice donor sequence (TT528/GTGAGG) within exon 4. Although reading frames appeared to be preserved in all three putative transcripts, significant portions of the presumed first and second transmembrane spans as well as the immediately following cytoplasmic domain would be deleted from the mutant CFTR polypeptides, if made. These observations are consistent with a loss of CFTR function in this cystic fibrosis patient.
High Performance Micro Resonators-Based Sensors Using Multimode Excitation (2022)

We present a multi-mode excitation technique to significantly amplify the amplitude signal of micro-resonators-based sensors operating at their higher-order modes. We show that the multi-mode excitation can significantly reduce the noise effects, elevate the dynamic response level, and amplify the total amplitude response. We demonstrate the efficiency of the multi-mode excitation to enhance the performance of a gas sensor using electrothermally heated doubly-clamped buckled beams. The results indicate clear amplification for the response at the 2nd mode while detecting Helium compared to a single-source excitation. A 24-times amplitude magnification is achieved. The demonstrated approach provides a promising path to efficiently exploit the higher-order modes of resonant gas sensors leading to improved accuracy and resolution.
Changes in genome content generated via segregation of non‐allelic homologs (2012)

A careful analysis of two maize recombinant inbred lines (RILs) relative to their inbred parents revealed the presence of several hundred apparently de novo copy number variants (CNVs). These changes in genome content were validated via both PCR and whole exome-array capture-and-sequencing experiments. One hundred and eighty-five genomic regions, which overlap with 38 high-confidence genes, exhibited apparently de novo copy number variation (CNV) in these two RILs and in many instances the same apparently de novo CNV events were observed in multiple RILs. Further analyses revealed that these recurrent apparently de novo CNVs were caused by segregation of single-copy homologous sequences that are located in non-allelic positions in the two parental inbred lines. F(1) individuals derived from these inbred lines will be hemizygous for each of these non-allelic homologs but RIL genotypes will contain these sequences at zero, one or two genomic loci. Hence, the segregation of non-allelic homologs may contribute to transgressive segregation. Indeed, statistical associations between phenotypic quantitative trait loci and genomic losses were observed for two of 14 tested pairs of non-allelic homologs.
Containers (2016)

The C++ Standard Library provides a selection of different data structures that you can use to store data. Containers work in tandem with algorithms, described in Chapter 4. Containers and algorithms are designed in such a way that they do not need to know about each other. The interaction between them is accomplished with iterators. All containers provide iterators, and algorithms only need iterators to be able to perform their work.
Hyperthermia protects mice against the lethal effects of endotoxin (1993)

Recently, investigators have reported that heat shock proteins (HSPs) can protect isolated cells from cytotoxicity induced by two important mediators of sepsis: interleukin-1 and tumor necrosis factor. The present study was undertaken to examine the hypothesis that transient whole body hyperthermia could decrease mortality from subsequent challenge with gram-negative endotoxin. We demonstrate that heat pretreatments improved long-term survival fivefold in a mouse endotoxin model and this was correlated with the production of HSPs. There was a marked difference in individual organ expression of the inducible 72-kDa heat shock protein (HSP72). Heat treatments caused significant HSP72 formation in lung, liver, kidney, and small intestine, but much lesser formation in heart, brain, and abdominal wall muscle. Additional experiments demonstrated that the protective effect of hyperthermic treatments against an endotoxin challenge occurred early, i.e., 1 and 2 h after heating, was maximal at 12 h, and had significantly diminished by 48 h. The formation and decay of HSP72 demonstrated a time course that paralleled the survival curve from endotoxin challenge, thus suggesting a possible role for HSP72 in the protective effect. Surprisingly, and in contrast to studies reported in incubated cells, endotoxin alone did not cause significant formation of HSP72 in vivo.
Macrophage depletion blocks congenital SARM1-dependent neuropathy (2022)

ABSTRACT Axon loss contributes to many common neurodegenerative disorders. In healthy axons, the axon survival factor NMNAT2 inhibits SARM1, the central executioner of programmed axon degeneration. We identified two rare NMNAT2 missense variants in two brothers afflicted with a progressive neuropathy syndrome. The polymorphisms result in amino acid substitutions, V98M and R232Q, which reduce NMNAT2 NAD + -synthetase activity. We generated a mouse model of the human syndrome and found that Nmnat2 V98M / Nmnat2 R232Q compound-heterozygous CRISPR mice survive to adulthood but develop progressive motor dysfunction, peripheral axon loss, and macrophage infiltration. These disease phenotypes are all SARM1-dependent. Remarkably, macrophage depletion therapy blocks and reverses neuropathic phenotypes in Nmnat2 V98M/R232Q mice, identifying a SARM1-dependent neuroimmune mechanism as a key driver of disease pathogenesis. These findings demonstrate that SARM1 induces an inflammatory neuropathy and highlight the potential of immune therapy to treat this rare syndrome and other neurodegenerative conditions associated with NMNAT2 loss and SARM1 activation.
Mechanism and modification of bradykinin-induced coronary vasodilation. (1975)

In isolated perfused rabbit hearts, bradykinin produced a concentration-dependent decrease in coronary resistance directly associated with biosynthesis and release of prostaglandin-E-like substance. An inhibitor of bradykinin destruction (the nonapeptide SQ-20881) markedly enhanced both the coronary vasodilation and release of prostaglandin-E-like substance produced by cardiac injection of bradykinin. Indomethacin inhibited both the myocardial prostaglandin biosynthesis and the decrease in coronary resistance induced by bradykinin. The demonstration that bradykinin is a potent stimulator of prostaglandin biosynthesis in the heart has implications as to the cause of the afferent cardiovascular reflexes and pain in myocardial infarction and angina pectoris.
Massive MIMO for interference management in heterogeneous networks (2014)

In this paper, a spatial interference coordination scheme for a typical macro/small-cell overlay scenarios is proposed which protects small-cell user equipments (UEs) from macro-cell interference and has potential applications in massive multiple-input multiple-output (MIMO) deployments. We assume the macro base stations (BSs) to be equipped with a large number of transmit antennas which are employed to reduce interference towards small-cell users by means of spatial transmit processing. Uncoordinated spatial multiplexing (SMUX) per access point (AP) is considered as a baseline, i.e. the macro BS uses zero-forcing (ZF)-based block diagonalization (BD) [1] to serve their user without taking interference towards small-cell UEs into account. The proposed method considers a joint BD/interference-alignment (IA) - approach to calculate the macro pre-coder and reduces the dimension of the interference sub-space for small-cell UEs without destroying the orthogonality of the macro BD. It results, that the the interference can be reduced even if the number of protected small-cell UEs exceeds the number of free spatial dimensions at the macro BS.
Crystal structure of cis-bis-(N-isopropyldithiocarbamato)nickel(II) (1974)

The crystal structure of the title compound, has been established by Patterson and Fourier methods from single-crystal photographic X-ray diffraction data, and was refined by full-matrix least-squares to R 0·09 (673 reflections). Crystals are trigonal, space group Rc, a= 22·13(1), c= 15·06(3)Å, Z= 18.The structure is the first example of a square-planar bis(dithiocarbamato) complex with different ligand substituents to adopt the cis-conformation in the solid; this imposes a marked distortion on the NiS4 molecular core and is due to strong hydrogen bonding forces between the –NH– hydrogen and sulphur atoms of adjoining molecules, the overall molecular packing being a cylindrical array down c.