gebhart/patrepeval huggingface dataset:
Selective Encapsulation of Single Cells and Subcellular Organelles into Picoliter- and Femtoliter-Volume Droplets (2005)

This paper describes a method, which combines optical trapping and microfluidic-based droplet generation, for selectively and controllably encapsulating a single target cell or subcellular structure, such as a mitochondrion, into a picoliter- or femtoliter-volume aqueous droplet that is surrounded by an immiscible phase. Once the selected cell or organelle is encased within the droplet, it is stably confined in the droplet and cannot be removed. We demonstrate in droplet the rapid laser photolysis of the single cell, which essentially "freezes" the state that the cell was in at the moment of photolysis and confines the lysate within the small volume of the droplet. Using fluorescein di-beta-d-galactopyranoside, which is a fluorogenic substrate for the intracellular enzyme beta-galactosidase, we also assayed the activity of this enzyme from a single cell following the laser-induced lysis of the cell. This ability to entrap individual selected cells or subcellular organelles should open new possibilities for carrying out single-cell studies and single-organelle measurements.
Signalment, Survival, and Prognostic Factors in Doberman Pinschers With End-Stage Cardiomyopathy (1997)

Congestive heart failure (CHF) was evaluated by retrospective review of case records of 66 Doberman Pinschers presenting with overt signs of 2 weeks' duration or less. Left-sided CHF was predominant, the majority of dogs were male, most were 5 to 10 years of age, and CHF tended to occur in females at an older age. Sudden death occurred in 13 dogs (20%). The mean and median survival times of all dogs were 9.65 and 6.5 weeks, respectively. Both atrial fibrillation and bilateral CHF at the time of presentation were associated with significantly shorter survival times.
Oriented Nucleation of β-Hematin Crystals Induced at Various Interfaces: Relevance to Hemozoin Formation (2008)

The nucleation of malaria pigment (hemozoin) and β-hematin crystals (synthetic hemozoin) can be promoted by lipid molecules. To determine the orientation of β-hematin crystals nucleated by 1-myristoyl-glycerol (MMG) on the water surface, we undertook a grazing incidence synchrotron X-ray diffraction and X-ray reflectivity study. Our results indicate that premixed α-hematin with MMG yielded β-hematin nanocrystals oriented with the {100} face parallel to water surface, which we explain insofar that the spreading solution allows MMG molecular aggregation into clusters exposing OH groups and oxygen lone-pair electrons that interact with hematin molecules. Hematin molecules, which did not interact with MMG clusters, do not yield β-hematin, but rather an unknown crystalline phase. Independently, evidence is presented that self-assembled functionalized alkanethiol monolayers (SAMs) exposing OH groups induce β-hematin nucleation primarily via its {100} face, whereas those exposing CH3 induce nucleation of either the {100} or {010} face, preferentially {010}. The results can be explained in terms of a difference in affinity of the SAMs to these two crystal faces. The two sets of β-hematin nucleation experiments, conducted under different conditions, strengthen the notion that MMG molecules, mimicking a digestive vacuole lipid surface, induce, via stereospecific interactions, oriented nucleation of β-hematin at the {100} face.
Sensors for glucose monitoring: technical and clinical aspects (2001)

The aim of this article is to critically discuss the technical and clinical aspects of glucose sensors and to briefly review current technical developments. This includes sensors for spot glucose measurements as well as those used for continuous glucose monitoring. Continuous glucose monitoring in particular should supply the diabetic patient with all the information required to optimize insulin therapy and metabolic control. Such systems should also allow hypo- and hyperglycemic episodes to be avoided. During the last 30 years numerous attempts have been made to develop glucose sensors, and new major breakthroughs have been announced repeatedly. However, up until now no glucose sensor has been available that can be used by diabetic patients in daily life conditions. Also one type of glucose sensor, a glucose electrode, recently received approval by the Food and Drug Administration (USA) and is commercially available. Other glucose sensors employing the transdermal, microdialysis or open tissue microperfusion technique are currently under clinical development and may also become available in the near future. The types of glucose sensors referred to so far are not truly non-invasive, but only minimally invasive. They measure glucose concentration in the interstitial fluid of the skin or the subcutis. Non-invasive optical glucose sensors are designed to monitor glucose changes in the skin by directing light through it. They measure the characteristics of the reflected light that are changed as the result of an interaction with glucose. However, none of the attempts with optical glucose sensors have resulted thus far in the development of a sensor that allows monitoring of glucose with sufficient accuracy and precision within the clinically relevant glucose range in daily life conditions. Nevertheless, more minimal-invasive glucose sensors systems will become available for practical use in the near future, whereas it is still uncertain if this can be said for any non-invasive glucose sensor.
Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions (2006)

The Polycomb group (PcG) proteins form chromatin-modifying complexes that are essential for embryonic development and stem cell renewal and are commonly deregulated in cancer. Here, we identify their target genes using genome-wide location analysis in human embryonic fibroblasts. We find that Polycomb-Repressive Complex 1 (PRC1), PRC2, and tri-methylated histone H3K27 co-occupy >1000 silenced genes with a strong functional bias for embryonic development and cell fate decisions. We functionally identify 40 genes derepressed in human embryonic fibroblasts depleted of the PRC2 components (EZH2, EED, SUZ12) and the PRC1 component, BMI-1. Interestingly, several markers of osteogenesis, adipogenesis, and chrondrogenesis are among these genes, consistent with the mesenchymal origin of fibroblasts. Using a neuronal model of differentiation, we delineate two different mechanisms for regulating PcG target genes. For genes activated during differentiation, PcGs are displaced. However, for genes repressed during differentiation, we paradoxically find that they are already bound by the PcGs in nondifferentiated cells despite being actively transcribed. Our results are consistent with the hypothesis that PcGs are part of a preprogrammed memory system established during embryogenesis marking certain key genes for repressive signals during subsequent developmental and differentiation processes.
Predicting Success in the Tactical Air Combat Party Training Pipeline (2011)

The results suggest that simple testing methods can identify candidates at high risk of failure.
Egress of varicella-zoster virus from the melanoma cell: a tropism for the melanocyte (1995)

The pathway of envelopment and egress of the varicella-zoster virus (VZV) and the primary site of viral production within the epidermal layer of the skin are not fully understood. There are several hypotheses to explain how the virus may receive an envelope as it travels to the surface of the monolayer. In this study, we expand earlier reports and provide a more detailed explanation of the growth of VZV in human melanoma cells. Human melanoma cells were selected because they are a malignant derivative of the melanocyte, the melanin-producing cell which originates in the neural crest. We were able to observe the cytopathic effects of syncytial formation and the pattern of egress of virions at the surfaces of infected monolayers by scanning electron microscopy and laser-scanning confocal microscopy. The egressed virions did not appear uniformly over the syncytial surface, rather they were present in elongated patterns which were designated viral highways. In order to document the pathway by which VZV travels from the host cell nucleus to the outer cell membrane, melanoma cells were infected and then processed for examination by transmission electron microscopy (TEM) at increasing intervals postinfection. At the early time points, within minutes to hours postinfection, it was not possible to localize the input virus by TEM. Thus, viral particles first observed at 24 h postinfection were considered progeny virus. On the basis of the TEM observations, the following sequence of events was considered most likely. Nucleocapsids passed through the inner nuclear membrane and acquired an envelope, after which they were seen in the endoplasmic reticulum. Enveloped virions within vacuoles derived from the endoplasmic reticulum passed into the cytoplasm. Thereafter, vacuoles containing nascent enveloped particles acquired viral glycoproteins by fusion with vesicles derived from the Golgi. The vacuoles containing virions fused with the outer plasma membrane and the particles appeared on the surface of the infected cell. Late in infection, enveloped virions were also present within the nuclei of infected cells; the most likely mechanism was retrograde flow from the perinuclear space back into the nucleus. Thus, this study suggests a role for the melanocyte in the pathogenesis of VZV infection, because all steps in viral egress can be accounted for if VZV subsumes the cellular pathways required for melanogenesis.
Calcium Depletion Modifies the Structure of the Photosystem II O2-Evolving Complex (2001)

A 5 min exposure of photosystem II to a pH 3 citric acid solution is a simple method for selective removal of Ca(2+) from the O(2)-evolving complex. The resulting preparation retains the 23 and 17 kDa extrinsic polypeptides, but the activity of this material is only 10-20% of that of an untreated control sample. Biochemical characterization of citrate-treated photosystem II reveals that some reaction centers lose the extrinsic proteins during citrate treatment. Furthermore, a comparison of photosystem II preparations treated with citrate, or depleted of 23 and 17 kDa extrinsic polypeptides by high-salt treatment, shows that low concentrations of a small reductant, NH(2)OH, which has little effect on the activity of intact photosystem II, can reduce and inhibit the Mn cluster in both types of preparations. In contrast, a large reductant, hydroquinone, cannot access the majority of O(2)-evolving centers in citrate-treated preparations, while 23 and 17 kDa-depleted material is rapidly inactivated by the reductant. Incubation of the citrate-treated samples in high ( approximately 60 mM) concentrations of CaCl(2) restores 50% of the lost activity; this Ca(2+)-reconstituted activity is chelator-insensitive, indicating that rebinding of Ca(2+) restores the structural integrity of the O(2)-evolving complex. A characterization of Ca(2+) and Cl(-) affinities in steady-state activity assays shows that citrate-treated preparations exhibit a Cl(-) requirement similar to that of polypeptide-depleted photosystem II, while Ca(2+) reactivation of O(2) evolution appears to occur at two structurally distinct sites. One site exhibits a high Ca(2+) affinity, similar to that found in polypeptide-depleted samples, but a second, lower-affinity site also exists, with a K(M) that is approximately 10 times greater than that of the high-affinity site, which is associated with centers that retain the extrinsic polypeptides. These data indicate that citrate-induced Ca(2+) depletion causes release of the 23 and 17 kDa extrinsic polypeptides from some photosystem II reaction centers, and also modifies the structure of the polypeptide-retaining O(2)-evolving centers so that the Mn cluster is exposed to small, but not large, reductants. This change may be due to subtle modifications to the structure of the photosystem II extrinsic proteins that produces a new pathway between the solvent and the Mn cluster or, alternatively, to the opening of an existing channel in the intrinsic lumenal polypeptide domain, between the solvent and the Mn cluster, that is normally occluded by a bound Ca(2+) atom.
Exploring the Potential Health Impact and Cost-Effectiveness of AIDS Vaccine within a Comprehensive HIV/AIDS Response in Low- and Middle-Income Countries (2016)

Even a modestly effective vaccine could contribute strongly to a sustainable response to HIV/AIDS and be cost-effective, even with optimistic assumptions about other interventions. Higher efficacy would provide even greater impact and cost-effectiveness, and would support broader access. Vaccine efficacy and cost per regimen are critical in achieving cost-effectiveness, with cost per regimen being particularly critical in low-income countries and at lower efficacy levels.
Retroviruses and AIDS (1985)

Lymphadenopathy Associated Virus (LAV) is one prototype viral isolate of the virus proposed as the cause of AIDS. In all cases of AIDS, it was possible to isolate LAV: sexually active male homosexuals, intravenous drug users, recipients of blood transfusions, hemophiliacs, Africans and Haitians. All isolates have the characteristics of a retrovirus. LAV is T4 lymphotropic and cytopathic for the T4 helper-inducer subset. The T4 molecule is involved in the cellular receptor for the virus. The seroepidemiological study shows a prevalence of IgG antibodies to LAV in patients with AIDS related complexes or AIDS. LAV was shown to be infectious for chimpanzees. The inactivation of LAV by chemical and physical agents is reported. LAV reverse transcriptase is strongly inhibited by an inhibitor of murine retroviruses, the ammonium 21 tungsto 9 antimoniate.
The Alkylating-HDAC Inhibition Fusion Principle: Taking Chemotherapy to the Next Level with the First in Class Molecule EDO-S101 (2015)

Chemotherapy may still be an essential component to treat cancer in combination with new targeted therapies. But chemotherapy needs to get smarter in order to make those combination regimens more effective and also more tolerable, particularly for an aging population. We describe the first time the synthesis and pharmacological testing of a fusion molecule comprising of the alkylator bendamustine and the HDAC-inhibitor vorinostat. The drug was designed to allow for the exploitation of both mechanisms of action simultaneously with the goal to provide a molecule with superior efficacy over the single agents. The pharmacological testing confirms the full functional capacity of both moieties and encouraging pharmacological data raises the hope that the drug may turn out to be a great addition to the armentarium of anticancer agents.
Domain-wall shift based multi-level MRAM for high-speed, high-density and energy-efficient caches (2013)

Spin Transfer Torque (STT) Magnetic Random Access Memory (MRAM) is a promising candidate for future on-chip memory, owing to its attractive features like non-volatility, high-density, and zero-leakage [1, 2]. However, the speed and reliability of the standard MRAM cell (1Transistor-1Resistor or 1T-1R cell shown in Fig. 1), are mainly limited by dielectric breakdown of the magnetic tunnel junction (MTJ) [1] under high write-current injection [3, 8] (Fig. 2). In recent years, several device solutions have been proposed that can mitigate this bottleneck by employing separate read and write paths, thereby avoiding write-current injection into the tunneling oxide. Nonlocal-STT [4], Spin-Hall Effect [5], and domain-wall-shift (DWS) [6-8] are three such write mechanisms. We have observed that DWS can be highly energy-efficient and robust, owing to low-voltage, low-current magnetization switching and high cell TMR (tunnel magneto-resistance ratio [1]) [4-6]. However, such bit-cells, with isolated read and write ports, are bound to use two access transistors (Fig. 3), resulting in significant area-penalty. In this work, we propose a multi-level MRAM (ML-MRAM) bit-cell based on DWS that can store 2-bits of data per-cell and can therefore achieve a factor of ~2x reduction in area, read latency as well as read energy (which dominates the total energy consumption) as compared to a DWS-based single-bit-cell. The proposed bit-cell can outperform the standard 1T-1R MRAM (Fig. 1), by a factor of ~2x in terms of area, read-latency, read-energy and by 8x and 4x in terms of write-energy and read disturb margin respectively, apart from mitigating the reliability issues related to dielectric-breakdown. Due to the possibility of sub-nano-second read/write operations, the proposed multi-level bit-cell can be suitable for all levels of the cache hierarchy, including L1 caches (in contrast, previous MRAM proposals have focused on the lower-level caches, which have less stringent speed requirements).
The delineation of a decapeptide gonadotropin-releasing sequence in the carboxyl-terminal extension of the human gonadotropin-releasing hormone precursor. (1986)

The human gonadotropin-releasing hormone (GnRH) precursor consists of the GnRH sequence followed by a 59-amino acid carboxyl-terminal extension. A 56-amino acid peptide within this extension has been shown to stimulate gonadotropin release, and this activity has been localized to its amino-terminal region. A series of seven overlapping peptide fragments corresponding to the first 24 amino acids of the carboxyl-extension of the GnRH precursor were synthesized and tested for their ability to stimulate luteinizing hormone and follicle-stimulating hormone release from cultured human anterior pituitary cells. All active peptide fragments were found to incorporate the decapeptide sequence Asn-Leu-Ile-Asp-Ser-Phe-Gln-Glu-Ile-Val which is regarded as a minimal structural requirement delineated for gonadotropin-releasing activity. A further flanking sequence extending this active region from its carboxyl terminus was found to enhance gonadotropin-releasing activity although the flanking sequence itself was inactive. The gonadotropin release stimulated by the active peptides wa shown to be a dose- dependent, specific, and calcium-dependent phenomenon which occurred independently of the GnRH receptor on the pituitary gonadotrophs as a GnRH antagonist did not inhibit activity.
Defining Incident Vertebral Deformity: A Prospective Comparison of Several Approaches (1999)

Vertebral deformities are common and important outcomes in clinical trials and epidemiologic studies of osteoporosis. While several different methods for defining new deformities have been proposed, it is not clear which is best. We used data from serial spine radiographs obtained an average of 3.7 years apart in 7238 women age >/=65 years from the Study of Osteoporotic Fractures to compare several approaches to defining new deformities by morphometry including a fixed percentage reduction in any vertebral height (FIXED%), a change in a summary spinal deformity index, a change in a vertebra from no prevalent deformity at baseline to a deformity at follow-up, as well as several variations of these methods. We compared results of each definition with several clinical correlates, including height loss, back pain, age, baseline bone mineral density, and the presence of a baseline deformity. We also estimated the sample size required for a clinical trial using various cut points. At a given level of incidence, all methods had similar relationships with each of the correlates. Given that similarity, the FIXED% method was simplest and needed no reference data. Using the FIXED% method, a 20-25% vertebral height reduction criterion for deformity maximized the power for a clinical trial. We conclude that all of the morphometric approaches to defining incident deformities have similar relationships to clinical correlates of vertebral deformity, but that use of a fixed percentage reduction in vertebral height is the simplest and most practical. For the FIXED% method, a 20-25% reduction in vertebral height minimizes the sample size required for clinical trials and epidemiologic studies.
Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma (2015)

Among patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.).
Skin blood flow in humans as a function of environmental temperature measured by ultrasound (1980)

We have measured the blood velocities in arteries supplying the skin in humans both in areas with arteriovenous anastomoses (AVA) and in skin areas without AVA in different temperature situations by means of a pulsed, bidirectional doppler ultrasound instrument. The instrument measures the time average of the instantaneous mean of the blood velocities present in a cross-section of a vessel. So long as the cross-sectional area of the vessel is constant, this average velocity is proportional to volume flow. We observe rapid and large fluctuations in blood velocities in arteries supplying skin areas with AVA in a comfortably warm environment. These fluctuations are substantially larger and more rapid than described by previous authors who have used plethysmograph methods. The blood velocities are more constant both at higher and lower environmental temperatures. There are no similar fluctuations in blood velocity in arteries supplying skin areas without AVA.
Molecular mimicry of host sialylated glycans allows a bacterial pathogen to engage neutrophil Siglec-9 and dampen the innate immune response (2009)

Human neutrophil Siglec-9 is a lectin that recognizes sialic acids (Sias) via an amino-terminal V-set Ig domain and possesses tyrosine-based inhibitory motifs in its cytoplasmic tail. We hypothesized that Siglec-9 recognizes host Sias as "self," including in cis interactions with Sias on the neutrophil's own surface, thereby dampening unwanted neutrophil reactivity. Here we show that neutrophils presented with immobilized multimerized Siaalpha2-3Galbeta1-4GlcNAc units engage them in trans via Siglec-9. The sialylated capsular polysaccharide of group B Streptococcus (GBS) also presents terminal Siaalpha2-3Galbeta1-4GlcNAc units, and similarly engages neutrophil Siglec-9, dampening neutrophil responses in a Sia- and Siglec-9-dependent manner. Reduction in the neutrophil oxidative burst, diminished formation of neutrophil extracellular DNA traps, and increased bacterial survival are also facilitated by GBS sialylated capsular polysaccharide interactions with Siglec-9. Thus, GBS can impair neutrophil defense functions by coopting a host inhibitory receptor via sialoglycan molecular mimicry, a novel mechanism of bacterial immune evasion.