Miracle-dz/UniFAR-FTUs huggingface dataset:
Changes in Refraction during Life *

IT is well known that the refraction of the eyes may change in the course of a lifetime, but we do not know the reasons and the rhythm that rule such changes of shape and function. The interest of research workers has long been exclusively focused on the question of the origin of short-sightedness. On this there are two opinions: the endogenous theory that considers the germ-plasma as the basis for the development of the eye and its parts, and the exogenous theory that attributes short-sightedness to the observation of close objects and other mechanical factors. If we talk of refraction we mean total refraction. However, this does not mean a degree which is directly measurable, but a figure that results from the proportion of all optical constant values to the length of the eye's axes. This fact and the approximate value of any subjective measurement explain the difficulties that hinder work in this field. The first step was an investigation of the frequency of different stages of refraction among certain sections of the population. Long-sightedness and short-sightedness, like all biological characteristics, exist in innumerable finely graduated degrees. The proportion of the different states of refraction found at various stages of life confirm that myopia increases more rapidly in the course of the school years than later in life. Until recently it has been maintained that learning to read and write is the chief cause of the development of myopia. In contrast to the study of large-scale statistics, the investigation of refraction-changes during the lives of individuals has a more personal character. It is an important condition that a series of patients should visit the same oculist over a long period.
Evaluating fault lines in Aliso Canyon

The Aliso Canyon methane storage field, which has been in use for four decades, is perilously situated across the Santa Susana fault ([ 1 ][1]). However, SoCalGas (the operator of Aliso) and California state regulators began to assess the risks of the location only after the disastrous 2015 methane
Optimal dual frames for uniform frames with erasures

Given a frame as a coder, its optimal dual as encoder can make the reconstruction error arising from erasure minimum. According to the eigenvalues of the frame operator, we give some sufficient conditions under which the unique optimal dual frame can be identified. Firstly for a Unit-form frame, if the eigenvalues of frame operator |λi| equal to a constant, the canonical dual is the only optimal dual. Secondly, for a uniform frame, if the eigenvalues of frame operator |λi| equal to a constant, the canonical dual is the unique optimal dual. Finally, when we consider the probability of data loss, we will find that if the eigenvalues of frame operator |λi| equal to a constant, the canonical dual is the only probability optimal dual. As an application, we give the examples to show the effectiveness of the theorems we proposed.
Use of Specialty OB Consults During High-Risk Pregnancies in a Medicaid-Covered Population

This study examines the impact of a Medicaid-supported intervention (Antenatal and Neonatal Guidelines, Education and Learning System) to expand a high-risk obstetrics consulting service on the use of specialty consults between 2001 and 2006. Using a Medicaid claims-birth certificate data set, we find a decline over time in use of specialty consults for lower risk diagnoses and a shift to remote modalities for contact. Local physician participation in grand rounds via teleconference was associated both with specialty contact and use of remote modalities. Local physician use of a Call Center service was also associated with patient specialty contact. Expansion of telemedicine remote sites did not increase the likelihood of contact but was associated with the shift toward remote modalities. Specialty consult use and modality were influenced by the care context of the patient, particularly level of pregnancy risk, the specialty of the primary prenatal care provider, the timing of her prenatal care, and her ethnicity and education level.
Brexit and European science

The United Kingdom's vote in favor of leaving the European Union (EU) has considerable ramifications for science. As the UK negotiates its “Brexit,” there is recognition that research is crucial to long-term economic success and that Europe needs a strong knowledge and innovation system to compete internationally and tackle challenges such as climate change and improved health care. It would be unacceptable to allow Brexit to jeopardize this.
Treatment of Massive Hemoptysis Occurred from Destroyed Lung: Prevention of Contralateral Aspiration Using Endobronchial Blocker Followed by Pneumonectomy

Untreated massive hemoptysis, especially in patients with tuberculous-destroyed lung, is a serious complication resulting in considerable morbidity and mortality. We report a case of a patient who had active tuberculosis and a destroyed left lung with massive bleeding. He was transferred to our clinic with intubation of a right-sided Robertshaw double lumen tube and right upper lobe collapse likely due to tube malposition that was presented on chest X-ray. Because hemoptysis had persisted after bronchial arterial embolizaton, we replaced the double lumen tube with a conventional endotracheal tube and inserted an endobronchial blocker into the left main bronchus through an endotracheal tube guided by bronchoscopy to prevent aspiration of blood into the right lung. Left pneumonectomy was performed and hemotpysis was ceased. We suggest that the use of an endobronchial blocker followed by surgery may be a safe and effective modality of treatment in patients with persistent bleeding after bronchial arterial embolization.
Mediator and RNA polymerase II clusters associate in transcription-dependent condensates

Phase separation and gene control Many components of eukaryotic transcription machinery—such as transcription factors and cofactors including BRD4, subunits of the Mediator complex, and RNA polymerase II—contain intrinsically disordered low-complexity domains. Now a conceptual framework connecting the nature and behavior of their interactions to their functions in transcription regulation is emerging (see the Perspective by Plys and Kingston). Chong et al. found that low-complexity domains of transcription factors form concentrated hubs via functionally relevant dynamic, multivalent, and sequence-specific protein-protein interaction. These hubs have the potential to phase-separate at higher concentrations. Indeed, Sabari et al. showed that at super-enhancers, BRD4 and Mediator form liquid-like condensates that compartmentalize and concentrate the transcription apparatus to maintain expression of key cell-identity genes. Cho et al. further revealed the differential sensitivity of Mediator and RNA polymerase II condensates to selective transcription inhibitors and how their dynamic interactions might initiate transcription elongation. Science, this issue p. eaar2555, p. eaar3958, p. 412; see also p. 329 Critical components of transcription machinery form stable, condensate-like, transcription-dependent clusters in cells. Models of gene control have emerged from genetic and biochemical studies, with limited consideration of the spatial organization and dynamics of key components in living cells. We used live-cell superresolution and light-sheet imaging to study the organization and dynamics of the Mediator coactivator and RNA polymerase II (Pol II) directly. Mediator and Pol II each form small transient and large stable clusters in living embryonic stem cells. Mediator and Pol II are colocalized in the stable clusters, which associate with chromatin, have properties of phase-separated condensates, and are sensitive to transcriptional inhibitors. We suggest that large clusters of Mediator, recruited by transcription factors at large or clustered enhancer elements, interact with large Pol II clusters in transcriptional condensates in vivo.
1H-MR-spektroskopische Bildgebung bei Patienten mit klinisch gesichertem Morbus Alzheimer.

PURPOSE To detect regional differences in accompanying metabolic changes, 1H-Magnetic Resonance Spectroscopic Imaging (MRSI) was performed in 16 patients with Alzheimer's disease (AD); the clinical diagnosis was based upon DSM-III-R and NINCDS-ADRDA guidelines. METHODS In the hippocampal region metabolic maps of the local distribution of N-acetylaspartate (NAA), choline (Cho), creatine compounds (P(Cr)) and lactate were determined. Ratios of Cho/NAA, (P)Cr/NAA and Cho/(P)Cr calculated from selected hippocampal spectra were compared to those from healthy volunteers (n = 17). RESULTS AD patients demonstrated an increase of Cho/NAA and (P)Cr/NAA ratios caused by increased choline compounds and decreased NAA. These alterations were observed in 11/12 cases in the hippocampal and in 7/12 in the temporo-occipital region. Hippocampal Cho/NAA ratios (0.56 +/- 0.19) were significantly elevated compared with controls (0.33 +/- 0.04; p < 0.0001). CONCLUSION The observed elevation of choline compounds in the hippocampus supports the hypothesis that alterations in the cholinergic system play an important role in Alzheimer's disease. The observed reduction of NAA is due to neuronal degeneration.
Alergia al látex. Manifestaciones clínicas en la población general y reactividad cruzada con alimentos

La alergia al latex en los ultimos anos ha adquirido una gran importancia medica, no solo para el personal sanitario sino tambien, aunque en menor medida, para la poblacion general, debido a su ubicuidad. Son multiples los objetos que manejamos en nuestra vida cotidiana que estan fabricados con latex, y que por tanto pueden suponer un riesgo para los pacientes alergicos a este material. Ademas del personal sanitario, existe otro subgrupo de pacientes en los que la alergia al latex tiene una mayor incidencia que en la poblacion general; se trata de los pacientes multintervenidos, y especialmente los ninos con espina bifida y mielomeningocele. Las manifestaciones clinicas de alergia al latex, abarcan un amplio abanico: dermatitis de contacto, urticaria, angioedema, rinoconjuntivitis, asma y en ocasiones anafilaxia, dependiendo la presencia de una u otra clinica de la via de contacto con el latex y tambien del tiempo de exposicion al mismo. Ademas como ocurre con otros aeroalergenos, existen multiples reactividades cruzadas con alimentos, por lo que los pacientes alergicos al latex en muchas ocasiones asocian alergias alimentarias que se deben diagnosticar, ya que su desconocimiento puede suponer un riesgo anadido para el paciente.
Preschool Children’s Cardiac Reactivity Moderates Relations Between Exposure to Family Violence and Emotional Adjustment

This study examined relations between cardiac reactivity, family violence exposure (i.e., child maltreatment [CM] and inter-partner violence [IPV]), and preschool children’s emotional adjustment. A sample of 92 mother–preschooler dyads was drawn from predominantly low-income, rural communities. Dyads participated in a laboratory session in which children’s Electrocardiograph (ECG) monitoring occurred during a resting baseline, joint-challenge, and individual emotional and cognitive tasks. Mothers consented to review of Children & Youth Services (CYS) records for CM and completed an IPV measure. Mothers rated children’s emotional adjustment, and observers rated children on their frustration and positive affect. Children’s vagal suppression was shown to moderate relations between family violence exposure and emotional adjustment. Findings indicated that children greater in vagal suppression showed better emotional adjustment when from families low in violence. However, regardless of children’s level of vagal suppression, all children showed poorer emotional adjustment when from families high in violence.
CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity

Taking CRISPR technology further CRISPR techniques are allowing the development of technologies for nucleic acid detection (see the Perspective by Chertow). Taking advantages of the distinctive enzymatic properties of CRISPR enzymes, Gootenberg et al. developed an improved nucleic acid detection technology for multiplexed quantitative and highly sensitive detection, combined with lateral flow for visual readout. Myhrvold et al. added a sample preparation protocol to create a field-deployable viral diagnostic platform for rapid detection of specific strains of pathogens in clinical samples. Cas12a (also known as Cpf1), a type V CRISPR protein, cleaves double-stranded DNA and has been adapted for genome editing. Chen et al. discovered that Cas12a also processes single-stranded DNA threading activity. A technology platform based on this activity detected human papillomavirus in patient samples with high sensitivity. Science, this issue p. 439, p. 444, p. 436; see also p. 381 Single-stranded DNase activity upon guide RNA–dependent DNA binding can be harnessed for rapid and specific nucleic acid detection. CRISPR-Cas12a (Cpf1) proteins are RNA-guided enzymes that bind and cut DNA as components of bacterial adaptive immune systems. Like CRISPR-Cas9, Cas12a has been harnessed for genome editing on the basis of its ability to generate targeted, double-stranded DNA breaks. Here we show that RNA-guided DNA binding unleashes indiscriminate single-stranded DNA (ssDNA) cleavage activity by Cas12a that completely degrades ssDNA molecules. We find that target-activated, nonspecific single-stranded deoxyribonuclease (ssDNase) cleavage is also a property of other type V CRISPR-Cas12 enzymes. By combining Cas12a ssDNase activation with isothermal amplification, we create a method termed DNA endonuclease-targeted CRISPR trans reporter (DETECTR), which achieves attomolar sensitivity for DNA detection. DETECTR enables rapid and specific detection of human papillomavirus in patient samples, thereby providing a simple platform for molecular diagnostics.
Translocation of a gut pathobiont drives autoimmunity in mice and humans

Bacterial involvement in autoimmunity The composition of the commensal microbiota is known to influence autoimmune disease development and persistence. Manfredo Vieira et al. identified a gut microbe, Enterococcus gallinarum, that translocates from the gut into the organs of mice with a genetic predisposition to lupus-like autoimmunity (see the Perspective by Citi). Molecular signatures of gut barrier disintegration and pathogenic T helper cells were evident in the gut, liver, and lymphoid organs during colonization with the pathobiont. The ensuing pathology could be reversed by vancomycin treatment and by vaccination against E. gallinarum. The same bug was also found in liver biopsies of autoimmune patients, but not in healthy controls. Science, this issue p. 1156; see also p. 1097 Enterococcus gallinarum is implicated in the exacerbation of autoimmune pathology in genetically predisposed mice and humans. Despite multiple associations between the microbiota and immune diseases, their role in autoimmunity is poorly understood. We found that translocation of a gut pathobiont, Enterococcus gallinarum, to the liver and other systemic tissues triggers autoimmune responses in a genetic background predisposing to autoimmunity. Antibiotic treatment prevented mortality in this model, suppressed growth of E. gallinarum in tissues, and eliminated pathogenic autoantibodies and T cells. Hepatocyte–E. gallinarum cocultures induced autoimmune-promoting factors. Pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by an intramuscular vaccine targeting the pathobiont. E. gallinarum–specific DNA was recovered from liver biopsies of autoimmune patients, and cocultures with human hepatocytes replicated the murine findings; hence, similar processes apparently occur in susceptible humans. These discoveries show that a gut pathobiont can translocate and promote autoimmunity in genetically predisposed hosts.
Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation

A path to multidrug resistance Permeability glycoprotein (PgP) uses the energy from adenosine triphosphate (ATP) hydrolysis to transport substrates out of the cell. Many of its substrates are drugs, so it plays an important role in drug resistance. Structures in the inward-facing conformation have been determined for mouse, yeast, and algal PgP. Kim and Chen present the cryo–electron microscopy structure of human PgP in an outward-facing conformation. Two ATP molecules are bound between two nucleotide-binding domains. The substrate-binding site, located in the transmembrane domain, is open to the outside of the cell, but compressed, and no substrate is bound. This suggests that ATP binding, rather than ATP hydrolysis, promotes the transition to the outward-facing conformation and substrate release. Science, this issue p. 915 The structure of a key drug-efflux membrane protein reveals features that enable substrate translocation and release. The multidrug transporter permeability (P)–glycoprotein is an adenosine triphosphate (ATP)–binding cassette exporter responsible for clinical resistance to chemotherapy. P-glycoprotein extrudes toxic molecules and drugs from cells through ATP-powered conformational changes. Despite decades of effort, only the structures of the inward-facing conformation of P-glycoprotein are available. Here we present the structure of human P-glycoprotein in the outward-facing conformation, determined by cryo–electron microscopy at 3.4-angstrom resolution. The two nucleotide-binding domains form a closed dimer occluding two ATP molecules. The drug-binding cavity observed in the inward-facing structures is reorientated toward the extracellular space and compressed to preclude substrate binding. This observation indicates that ATP binding, not hydrolysis, promotes substrate release. The structure evokes a model in which the dynamic nature of P-glycoprotein enables translocation of a large variety of substrates.
On the design of path delay fault testable combinational circuits

A theoretical framework for investigating the design for the path-delay-fault testability problem is provided. Necessary and sufficient conditions for the existence of general robust tests in a multioutput, multilevel circuit are given. The conditions for the existence of a more restricted class of robust tests are derived from those for general robust tests. A design procedure is given for the synthesis of multioutput, multilevel combinational logic circuits in which all path delay faults are robustly detectable. A powerful factorization method, that of extended factorization, was exploited for this purpose. <<ETX>>
When did modern humans leave Africa?

A ∼180,000-year-old fossil from Israel provides evidence for early forays of Homo sapiens into western Asia The skeletal features of our species, Homo sapiens, include a globular braincase, brow ridges that are divided into central and side portions, a flat and retracted midface, a chin on the lower jaw, and a narrow pelvis. Fossils showing many of these characteristics have been excavated from the Ethiopian sites of Omo Kibish and Herto, dated at ∼195,000 and ∼160,000 years ago, respectively (1). Possible more primitive members of the species are known from Jebel Irhoud (Morocco) and Florisbad (South Africa), dated at ∼315,000 and ∼259,000 years ago, respectively (1). Yet, the oldest known H. sapiens fossils outside of Africa, from Skhul and Qafzeh in Israel, have been dated to just 90,000 to 120,000 years old. On page 456 of this issue, Hershkovitz et al. (2) provide fossil evidence from Misliya Cave, Israel, suggesting that our species had already left Africa by ∼180,000 years ago (see the figure).
Scheduling with rollback constraints in high-level synthesis of self-recovering ASICs

The authors develop software mechanisms for incorporating on-chip self-recovery-using checkpointing and rollback-during high-level synthesis. They propose an algorithm for rollback point insertion to minimize rollback overhead. It identifies good rollback points by successively eliminating clock cycle boundaries that are either expensive or violate the recovery time constraint. Only the minimum number of rollback points are inserted. A flexible synthesis methodology is presented in which rollback point insertion can precede, succeed, or be intertwined with scheduling. A novel edge-based scheduling algorithm is described that schedules edges to clock cycle boundaries, in addition to scheduling nodes to clock cycles. The system has been used to schedule flow graphs from the literature. Experimental results are presented. <<ETX>>
Sex reversal following deletion of a single distal enhancer of Sox9

Sox9 regulation during sex determination Sex determination is regulated by the Sox9 gene. During testis differentiation, this gene is directly targeted by the product of the Y chromosome–encoded gene Sry. The regulatory region of Sox9 is complex, which is typical of genes with multiple roles in development. Gonen et al. find that a single far-upstream 557–base pair element is critical for up-regulating Sox9. Without it, XY mice develop as females instead of males. The 557–base pair enhancer is conserved, likely to be relevant to human disorders of sex differentiation, and probably essential because it acts early in a time-critical process, and any failure allows ovary-specific factors to dominate. Science, this issue p. 1469 A single early-acting enhancer within a complex regulatory region is crucial for the role of Sox9 in testis determination. Cell fate decisions require appropriate regulation of key genes. Sox9, a direct target of SRY, is pivotal in mammalian sex determination. In vivo high-throughput chromatin accessibility techniques, transgenic assays, and genome editing revealed several novel gonadal regulatory elements in the 2-megabase gene desert upstream of Sox9. Although others are redundant, enhancer 13 (Enh13), a 557–base pair element located 565 kilobases 5′ from the transcriptional start site, is essential to initiate mouse testis development; its deletion results in XY females with Sox9 transcript levels equivalent to those in XX gonads. Our data are consistent with the time-sensitive activity of SRY and indicate a strict order of enhancer usage. Enh13 is conserved and embedded within a 32.5-kilobase region whose deletion in humans is associated with XY sex reversal, suggesting that it is also critical in humans.
Local injection of TGF-β increases the strength of tibial fractures in the rat

The effect of Transforming Growth Factor beta (TGF-beta) administered locally around the fracture line of healing rat tibial fractures was investigated after 40 days of healing. TGF-beta in a dose of 4 ng or 40 ng was injected every second day during the healing period. The strength, stiffness, energy absorption and deflection of the fractures were measured in a materials-testing machine. Compared with placebo-treated animals, the ultimate load of the fractures increased in the group injected with 40 ng of TGF-beta, but not in those injected with 4 ng. TGF-beta induced a dose-dependent increase in the cross-sectional area of the callus and bone at the fracture line. Consequently, local treatment of fractures with TGF-beta increases the callus formation and strength. The energy absorption and deflection capacities of the healing fractures are preserved.